Our Foundational Trials Collection provides a set of contempory trials upon which modern critical care is based. This is an excellent starting point for those new to the field, those preparing for exams and those wishing to refresh their knowledge.

This collection combines brief summaries of the trials, with critique and commentary. These are not a substitute for reading the original paper, but helps put each trial in context.

This collection is not yet complete and we're working hard to finish it this month. Of course, trial selection is subjective and others may chose different trials. The aim of this Collection is to provide a set of trials which provide the foundation of modern practice. For a complete set of important critical care trials, check out the "Trials" section on the menu.

We'll be publishing more collections over the next several months.

added January 22nd

By System

Neuro

KRESS

Kress. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000;342:1471-7

Eurotherm3235

Andrews. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury (Eurotherm3235 Trial). N Engl J Med 2015;373:2403-2412

CRASH

CRASH trial collaborators. Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 2004;364(9442):1321-1328

RESCUE-ICP

Hutchinson. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension (RESCUEicp). N Engl J Med 2016;375:1119-1130

IST

The International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke.1997;349(9065):1569-1581

ISAT

Molyneux. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002;360(9342):1267-74

NINDS rt-PA Stroke Study

The International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke. Lancet 1997;349(9065):1569-1581

CATIS

He. Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke. The CATIS Randomized Clinical Trial. JAMA 2014;311(5):479-489

MR CLEAN

Berkhemer. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke (MR CLEAN). N Engl J Med 2015;372:11-20

STICH

Medelow. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005;365:387-397

INTERACT2

Anderson. Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage (INTERACT 2). N Eng J Med 2013;368:2355-2365

Dutch Dexamethasone Meningitis Trial

de Gans. European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347(20):1549-1556

VA Status Epilepticus Study

Treiman. A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus. N Engl J Med 1998; 339:792-798

BEST-TRIP

Chesnut. A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury. New Engl J Med 2012;367:2471-2481

CRASH-3

The CRASH-3 Trial Collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomized, placebo-controlled trial. Lancet. 2019;394(10210):1713–23

DESTINY II

Jüttler. Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke (Destiny II). N Engl J Med 2014;370:1091-1100

SAHaRA

English. Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage. N Engl J Med 2025;392:1079-1088

British Aneurysm Nimodipine Trial

Pickard. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 1989;298(6674):636–642

NONSEDA

Olsen. Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients. N Engl J Med 2020; 382:1103-1111

ABC

Girard.Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial). Lancet 2008;371(9607):126-134

NASCIS III

Bracken. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study (NASCIS III). JAMA 1997;277(20):1597-604

INTREPID

Greer DM, Helbok R, Badjatia N, Ko SB, McKenna Guanci M, Sheth KN; for the INTREPID Study Group. Fever Prevention in Patients With Acute Vascular Brain Injury: The INTREPID Randomized Clinical Trial. JAMA. 2024;332(18):1525-1534

Circulatory

SAFE

2004

Finfer. A comparison of albumin and saline for fluid resuscitation in the intensive care unit (SAFE). N Engl J Med 2004;350(22):2247-56

CHEST

2012

Myburgh. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care (CHEST). NEJM 2012;367:1901-1911

6S

2012

Perner. Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis (6S). N Eng J Med 2012; 367:124-134

SMART

Semler. Balanced Crystalloids versus Saline in Critically Ill Adults (SMART). N Engl J Med 2018;378:829-839

PLUS

Finfer. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. N Engl J Med 2022;386:815-826

FLUID

McIntyre. A Crossover Trial of Hospital-Wide Lactated Ringer’s Solution versus Normal Saline. NEJM 2025;393:660-670

BICKELL

Bickell. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331:1105-1109

FEAST

Maitland. Mortality after Fluid Bolus in African Children with Severe Infection (FEAST Trial). N Engl J Med 2011

CLASSIC

Meyhoff. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med 2022;386:2459-2470

CLOVERS

The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. N Engl J Med 2023;388:499-510

SOAP II

De Backer. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl 2010;362:779-89

CATS

Annane. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomised trial. Lancet 2007;370:676-684

VAAST

Russell. Vasopressin versus norepinephrine infusion in patients with septic shock (VASST). NEJM 2008;358:877-87

DOREMI

Mathew. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N Engl J Med 2021; 385:516-525

IABP-SHOCK II

Thiele. Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock (IABP-SHOCK II Trial). NEJM 2012;367(14):1287-1296

DanGer Shock

Møller. DanGer Shock Investigators. Microaxial flow pump or standard care in infarct-related cardiogenic shock. N Engl J Med. 2024;390(15):1382-1393

ECLS-SHOCK

Thiele. Extracorporeal life support in infarct-related cardiogenic shock. N Engl J Med 2023;389(14):1286-1297

SEPSISPAM

Asfar. High versus low blood-pressure target in patients with septic shock. (SEPSISPAM). N Engl J Med 2014;370(17):1583-1593

PAC-Man

Harvey. Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial. Lancet 2006;366:472 - 477

EVERDAC

Muller. Deferring Arterial Catheterization in Critically Ill Patients with Shock. N Engl J Med 2025;393:1875-1888

Resuscitation

PARAMEDIC2

Perkins. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest (PARAMEDIC2). N Engl J Med 2018;epublished July 18th

ALPS

Kudenchuk. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med 2016;epublished April 4th

HACA

The Hypothermia after Cardiac Arrest Study Group. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest. N Engl J Med 2002; 346:549-556

Bernard

Bernard. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia. N Engl J Med 2002; 346:557-563

Olasveengen

Olasveengen. Intravenous Drug Administration During Out-of-Hospital Cardiac Arrest: A Randomized Trial. JAMA 2009;302(20):2222-2229

VAM-IHCA

Andersen. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest. A Randomized Clinical Trial. JAMA 2021;epublished September 29th

VSE-2

Mentzelopoulos SD, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, et al. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2013;310(3):270-279

European Epinephrine Study

Gueugniaud. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European epinephrine study group. N Engl J Med 1998;339(22):1595–601

Wenzel

Wenzel. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004;350:105–13

COCA

Vallentin. Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest. A Randomized Clinical Trial. JAMA 2021;326(22):2268-2276

PARAMEDIC-3

Couper. A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest. N Engl J Med 2025;392:336-348

IVIO

Vallentin. Intraosseous or Intravenous Vascular Access for Out-of-Hospital Cardiac Arrest. N Engl J Med 2024;epublished October 31st

PART

Wang. Effect of a Strategy of Initial Laryngeal Tube Insertion vs Endotracheal Intubation on 72-Hour Survival in Adults With Out-of-Hospital Cardiac Arrest. A Randomized Clinical Trial. JAMA 2018;320(8):769-778

AIRWAYS-2

Benger. Effect of a Strategy of a Supraglottic Airway Device vs Tracheal Intubation During Out-of-Hospital Cardiac Arrest on Functional Outcome. The AIRWAYS-2 Randomized Clinical Trial. JAMA 2018;320(8):779-791

CAAM

Jabre. Effect of Bag-Mask Ventilation vs Endotracheal Intubation During Cardiopulmonary Resuscitation on Neurological Outcome After Out-of-Hospital Cardiorespiratory Arrest (CAAM). A Randomized Clinical Trial. JAMA 2018;epublished February 27th

PARAMEDIC

2000

Perkins. Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial. Lancet 2014;epublished November 16th

LINC

Rubertsson. Mechanical Chest Compressions and Simultaneous Defibrillation vs Conventional Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest. The LINC Randomized Trial. JAMA 2013;311(1):53-61

DOSE VF

Cheskes. Defibrillation Strategies for Refractory Ventricular Fibrillation. N Engl J Med 2022;epublished November 6th

ARREST

Yannopoulos. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial. Lancet 2020;396(10265):1807-1816

Prague OOHCA Study

Belohlavek. Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest. A Randomized Clinical Trial. JAMA 2022;327(8):737-747

ARREST

Patterson. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial. Lancet 2023;402(10410):1329-1337

EXACT

Bernard. Effect of Lower vs Higher Oxygen Saturation Targets on Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest. The EXACT Randomized Clinical Trial. JAMA 2022;328(18):1818-1826

ANTHARTIC

François. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med 2019;381(19):1831-1842

TTM

Nielsen. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM study). N Engl J Med 2013;369:2197-2206

HYPERION

Lascarrou. Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. N Engl J Med N Engl J Med 2019;381:2327-2337

TTM2

Dankiewicz. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med 2021;384:2283-2294

BOX - Blood Pressure

Kjaergaard. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med 2022;387:1456-1466

BOX - Oxygenation

Schmidt. Oxygen Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med 2022;387:1467-1476

BOX - Fever Control

Hassager C, Schmidt H, Møller JE, Grand J, Mølstrøm S, Beske RP, et al. Duration of device-based fever prevention after cardiac arrest. N Engl J Med. 2023;388(10):888-897

TAME

Eastwood. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest. N Engl J Med 2023;389:45-57

COACT

Lemkes. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation (COACT). N Engl J Med 2019;2019;380:1397-1407

TOMAHAWK

Desch. Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation. N Engl J Med 2021;epublished August 29th

EMERGE

Hauw-Berlemont. Emergency vs Delayed Coronary Angiogram in Survivors of Out-of-Hospital Cardiac Arrest: Results of the Randomized, Multicentric EMERGE Trial. JAMA Cardiol 2022;7(7):700-707

Airway

IRIS

2000

Birenbaum. Cricoid Pressure Compared With a Sham Procedure in Rapid Sequence Induction of Anesthesia. JAMA Surg 2019;154;(1):9-17

BEAM

Driver. Effect of Use of a Bougie vs Endotracheal Tube and Stylet on First-Attempt Intubation Success Among Patients With Difficult Airways Undergoing Emergency Intubation. A Randomized Clinical Trial. JAMA 2018;319;(21):2179-2189

PREOXI

Gibbs. Noninvasive Ventilation for Preoxygenation during Emergency Intubation. N Engl J Med 2024;390:2165-2177

PreVent

Casey. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. N Engl J Med 2019;380:811-821

PrePARE

Janz. Effect of a fluid bolus on cardiovascularcollapse among critically ill adults undergoing tracheal intubation(PrePARE): a randomised controlled trial. Lancet Respir Med 2019;7(12):1039–47

MACMAN

Lascarrou. Video Laryngoscopy vs Direct Laryngoscopy on Successful First-Pass Orotracheal Intubation Among ICU Patients. A Randomized Clinical Trial. JAMA 2017;317;(5):483-493

TracMan

Young. Effect of Early vs Late Tracheostomy Placement on Survival in Patients Receiving Mechanical Ventilation: The TracMan Randomized Trial. JAMA 2013;309(20):2121

Terrangi

Terragni. Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients. JAMA 2010;303:1483–1489

AIRWAYS-2

Benger. Effect of a Strategy of a Supraglottic Airway Device vs Tracheal Intubation During Out-of-Hospital Cardiac Arrest on Functional OutcomeThe AIRWAYS-2 Randomized Clinical Trial. JAMA 2018;320(8):779-791

PART

Wang. Effect of a Strategy of Initial Laryngeal Tube Insertion vs Endotracheal Intubation on 72-Hour Survival in Adults With Out-of-Hospital Cardiac Arrest. A Randomized Clinical Trial. JAMA 2018;320(8):769-778

STYLETO

Jaber. Effect of the use of an endotracheal tube and stylet versus an endotracheal tube alone on first-attempt intubation success: a multicentre, randomised clinical trial in 999 patients. Intensive Care Med 2021;47:653-664

Check-UP

Semler. A multicenter, randomized trial of ramped position vs sniffing position during endotracheal intubation of critically ill adults. Chest 2017;152(4):712–22

CURASMUR

Guihard. Effect of Rocuronium vs Succinylcholine on Endotracheal Intubation Success Rate Among Patients Undergoing Out-of-Hospital Rapid Sequence Intubation. A Randomized Clinical Trial. JAMA 2019;322(23):2303-2312

CAAM

Jabre. Effect of Bag-Mask Ventilation vs Endotracheal Intubation During Cardiopulmonary Resuscitation on Neurological Outcome After Out-of-Hospital Cardiorespiratory Arrest (CAAM). A Randomized Clinical Trial. JAMA 2018;319(8):779-787

PREOXYFLOW

Vourc’h. High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive Care Med 2015;41:1538–1548

RSI

Casey. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. N Engl J Med 2025;epublished December 9th

KETASED

Jabre. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet 2009;374(9686):293-300

FLORALI2

Frat. Non-invasive ventilation versus high-flow nasal cannulaoxygen therapy with apnoeic oxygenation for preoxygenation be-fore intubation of patients with acute hypoxaemic respiratory fail-ure: a randomised, multicentre, open-label trial. Lancet Respir Med 2019;7(4):303–12

BOUGIE

Driver. Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation. A Randomized Clinical Trial. JAMA 2021;326;(24):2488-2497

PREPARE II

Russell. Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation (PREPARE II). A Randomized Clinical Trial. JAMA 2022;328(3):270-279

VODE

Geraghty. Video versus Direct Laryngoscopy for Urgent Intubation of Newborn Infants. N Engl J Med 2024;390:1885-1894

DEVICE

Prekker. Video versus Direct Laryngoscopy for Tracheal Intubation of Critically Ill Adults (DEVICE). N Engl J Med 2023;389:418-429

NICO

Freund. Effect of Noninvasive Airway Management of Comatose Patients With Acute Poisoning. A Randomized Clinical Trial. JAMA 2023;330;(23):2267-2274

PreVent 2

Treggiari. Hospital and long-term outcomes for subglottic suction and polyurethane cuff versus standard endotracheal tubes in emergency intubation (PreVent 2): a randomised controlled phase 2 trial. Lancet Respir Med 2025;epublished November 27th

Respiratory

ARMA

2000

The Acute Respiratory Distress Syndrome Network. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. N Engl J Med 2000; 342:1301-1308

PReVENT

Writing Group for the PReVENT Investigators. Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDSA Randomized Clinical Trial. JAMA 2018;320;(18):1872-1880

ALVEOLI

The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004;351:327-336

ART

ART Trial Investigators Writing Group. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome. A Randomized Clinical Trial (ART). JAMA 2017;318;(14):1335-1345

PROSEVA

Guérin. Prone Positioning in Severe Acute Respiratory Distress Syndrome (PROSEVA). New Engl J Med 2013;368:2159-2168

ACURASYS

Papazian. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107-1116

ROSE

The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome (ROSE trial). N Engl J Med 2019;2019;380:1997-2008

FACTT - Fluid

Wiedemann. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006; 354:2564-75

CESAR

Peek. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374: 1351-63

EOLIA

Combes. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA Trial). N Engl J Med 2018;378:1965-75

REST

McNamee. Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure. The REST Randomized Clinical Trial. JAMA 2021;epublished August 31st

OSCILLATE

Ferguson. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome (OSCILLATE). New Engl J Med 2013;epublished January 22rd

OSCAR

Young. High-Frequency Oscillation for Acute Respiratory Distress Syndrome (OSCAR). New Engl J Med 2013;epublished January 22nd

FLORALI

Frat. High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure (FLORALI study). N Eng J Med 2015;epublished May 17th

HIGH WEAN

Hernández. Effect of Postextubation High-Flow Nasal Cannula vs Noninvasive Ventilation on Reintubation and Postextubation Respiratory Failure in High-Risk PatientsA Randomized Clinical Trial. JAMA 2016;315(13):1354-1361

NIV for AECOPD

Brochard. Noninvasive Ventilation for Acute Exacerbations of Chronic Obstructive Pulmonary Disease. N Engl J Med 1995;333:817-822

UK-ROX

Martin. Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult PatientsThe UK-ROX Randomized Clinical Trial. JAMA 2025;334;(5):398-408

PILOT

Semler. Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation. N Engl J Med 2022;387:1759-1769

RENOVATE

RENOVATE Investigators and the BRICNet Authors. High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure. The RENOVATE Randomized Clinical Trial. JAMA 2025;333;(10):875-890

FAST

Burns. Frequency of Screening and Spontaneous Breathing Trial Techniques. A Randomized Clinical Trial. JAMA 2024;332;(21):1808-1821

TiP-Ex

Thille. Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece. N Engl J Med 2022;387:1843-1854

BREATHE

Perkins. Effect of Protocolized Weaning With Early Extubation to Noninvasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure. The Breathe Randomized Clinical Trial. JAMA 2018;320;(18):1881-1888

Gastrointestinal

WATERFALL

2022

de-Madaria. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. N Engl J Med 2022;387:989-1000

POINTER

Boxhoorn. Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis. N Engl J Med 2021;385:1372-1381

Villanueva

Villanueva. Transfusion Strategies for Acute Upper Gastrointestinal Bleeding. N Engl J Med 2013;368:11-21

HALT-IT

The HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet 2020;395(10241):1927-1936

REVISE

Cook. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med 2024;391:9-20

STOP-IT

Sawyer. Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection (STOP-IT trial). N Engl J Med 2015; 372:1996-2005

PEPTIC

The PEPTIC Investigators. Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical VentilationThe PEPTIC Randomized Clinical Trial. JAMA 2020;2020;323(7):616-626

GASTROSAM

Maitland. Intravenous Rehydration for Severe Acute Malnutrition with Gastroenteritis. NEJM 2025;epublished June 13th

SUP-ICU

Krag. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. N Engl J Med 2018;379:2199-2208

SuDDICU

SuDDICU Investigators. Selective decontamination of the digestive tract during ventilation in the ICU. N Engl J Med. 2025;epublished October 29th

Nutrition

PermiT

2015

Arabi. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults (PermiT). N Engl J Med 2015;372:2398-2408

Early PN trial

2013

Doig. Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition: A Randomized Controlled Trial. JAMA 2013;309(20):2130-2138

EPaNIC

Casaer. Early versus Late Parenteral Nutrition in Critically Ill Adults (EPaNIC). N Eng J Med 2011;365:506-517

PEPaNIC

Fivez. Early versus Late Parenteral Nutrition in Critically Ill Children (PEPaNIC). N Engl J Med 2016;374:1111-1122

CALORIES

Harvey. Trial of the Route of Early Nutritional Support in Critically Ill Adults (CALORIES). New Engl J Med 2014;371:1673-1684

Heidegger

Heidegger. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet 2012;381(9864)385-393

Reignier

Reignier. Effect of Not Monitoring Residual Gastric Volume on Risk of Ventilator-Associated Pneumonia in Adults Receiving Mechanical Ventilation and Early Enteral Feeding: A Randomized Controlled Trial. JAMA 2013;309(3):249

TARGET Protein

Summers. Augmented Enteral Protein During Critical Illness. The TARGET Protein Randomized Clinical Trial. JAMA 2025;epublished June 11th

RE-ENERGIZE

Heyland. A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries (RE-ENERGIZE). N Engl J Med 2022;87:1001-1010

REDOXS

Heyland. A randomized trial of glutamine and antioxidants in critically ill patients (REDOXS). N Engl J Med 2013;368:1489-1497

Liver

ATTIRE

2015

China. A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis. N Engl J Med 2021;384:808-817

Sort

Sort. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403–409

CONFIRM

Wong. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med 2021; 384:818-828

Keays

Keays. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ 1991;303:1026-1029

Lee

Lee. Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure. Gastroenterology 2009;137(3):856-864

STOPAH

Thursz. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015;372(17):1619‑1628

AntibioCor

Louvet. Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis. A Randomized Clinical Trial. JAMA 2023;329(18):1558-1566

REVERSE

Boyer TD, Sanyal AJ, Wong F, Frederick RT, Lake JR, O'Leary JG, et al. Terlipressin plus albumin is more effective than albumin alone in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1. Gastroenterology. 2016;150(7):1579-1589

BASS

Bass NM, Mullen KD, Sanyal AJ, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081

ELAD

Thompson J, Jones N, Al-Khafaji A, Malik S, Reich D, Munoz S, et al. Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: a multinational, prospective, controlled, randomised trial. Liver Transpl. 2018;24(3):380-393

HELIOS

Kribben A, Gerken G, Haag S, Herget-Rosenthal S, Treichel U, Betz C, et al; HELIOS Study Group. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology. 2012;142(4):782-789

RELIEF

Bañares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology. 2013;57(3):1153-1162

Renal

Hemodiafe

2000

Vinsonneau. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: A multicentre randomised trial. Lancet 2006; 368:379-385

RENAL

RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients (RENAL study). N Engl J Med 2009;361(17):1627-38

ATN

The VA/NIH Acute Renal Failure Trial Network. Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury. N Engl J Med 2008;359:7-20

STARRT-AKI

2001

The STARRT-AKI Investigators. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med 2020;383:240-251

RICH

Zarbock. Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury. A Randomized Clinical Trial. JAMA 2020;324(16):1629-1639

PROTECTION

Landoni. A Randomized Trial of Intravenous Amino Acids for Kidney Protection. N Eng J Med 2024;epublished June 12th

Renal Dose Dopamine

Bellomo. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000; 356: 2139-43.

BICARICU-2

Jung B, Jabaudon M, De Jong A, et al; BICARICU-2 Study Group. Sodium bicarbonate for severe metabolic acidemia and acute kidney injury: the BICARICU-2 randomized clinical trial. JAMA. 2025;334(22):2000-2010

Haematology

TRIC

2000

Hebert. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-17

REALITY

Ducrocq. Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia. The REALITY Randomized Clinical Trial. JAMA 2021;325(6):552-560

Villanueva

Villanueva. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368(1):11-21

HEMOTION

Turgeon.Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury. N Eng J Med 2024;391:722-735

SAHaRA

2001

English. Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage. N Engl J Med 2024;epublished December 9th

TRAIN

Taccone FS, Rynkowski Bittencourt C, Møller K, et al; TRAIN Study Group. Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury: The TRAIN Randomized Clinical Trial. JAMA. 2024;332(19):1623-1633

PROPPR

Holcomb. Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma: The PROPPR Randomized Clinical Trial. JAMA 2015;313(5):471

PAMPer

Sperry. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med 2018; 379:315-326

CRASH-2

Shakur. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010;376(9734):23–32

CRASH-3

The CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet 2019;394(10210):1713-1723

PATCH-Trauma

The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group. Prehospital Tranexamic Acid for Severe Trauma. N Engl J Med 2023;epublished June 14th

PROTECT

The PROTECT Investigators. Dalteparin versus Unfractionated Heparin in Critically Ill Patients. N Engl J Med 2011;364:1305-14

PREVENT

Arabi. Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis. N Engl J Med 2019;epublished February 18th

Sepsis

FEAST

Maitland. Mortality after Fluid Bolus in African Children with Severe Infection (FEAST Trial). N Engl J Med 2011;364:2483-2495

ANDROMEDA SHOCK 2

ANDROMEDA-SHOCK-2 Investigators. Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock—the ANDROMEDA-SHOCK-2 Randomized Clinical Trial. JAMA 2025;334;(22):1988-1999

CLASSIC

Meyhoff. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med 2022;386:2459-2470

CLOVERS

The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. N Engl J Med 2023;388:499-510

6S

Perner. Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis (6S). N Eng J Med 2012; 367:124-134

The first transfusion threshold trial in sepsis

ALBIOS

Caironi. Albumin Replacement in Patients with Severe Sepsis or Septic Shock (ALBIOS study). New Engl J Med 2014;370:1412-1421

Annane

Annane. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871

ADRENAL

Venkatesh. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL). N Engl J Med 2018;2018;378:797-808

APROCCHSS

Annane. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock (APROCCHSS). N Engl J Med 2018;378:809-818

TRISS

2001

Holst. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock. TRISS Trial Group and the Scandinavian Critical Care Trials Group. N Engl J Med 2014;371:1381-1391

CATS

Annane. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomised trial. Lancet 2007;370:676-684

VASST

Russell. Vasopressin versus norepinephrine infusion in patients with septic shock (VASST). NEJM 2008;358:877-87

Chastre

Chastre. Comparison of 8 vs. 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290:2588-2598

STOP-IT

Sawyer. Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection (STOP-IT trial). N Engl J Med 2015; 372:1996-2005

PRORATA

Bouadma. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomized controlled trial. Lancet. 2010;375:463-474

SEPSISPAM

Asfar. High versus low blood-pressure target in patients with septic shock. (SEPSISPAM). N Engl J Med 2014;370(17):1583-1593

LOVIT

Lamontagne.Intravenous vitamin C in adults with sepsis in the intensive care unit.N Engl J Med2022;386:2387–2398

PRORATA

Bouadma L, Luyt C-E, Tubach F, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010;375(9713):463-474

SCREEN

Arabi YM, Vishwakarma RK, Al-Dorzi HM, Al Mofleh A, Murthy S, Bihari S, et al; SCREEN Trial Group. Electronic sepsis screening among patients admitted to hospital wards: a stepped-wedge cluster randomized trial. JAMA. 2025 Mar 4;333(9):763-773

SONIA

Lucinde RK, Gathuri H, Mwaniki P, et al. A pragmatic trial of glucocorticoids for community-acquired pneumonia. N Engl J Med. 2025;393(22):2187-2197

BLING III

Dulhunty JM, Brett SJ, De Waele JJ, et al; BLING III Study Investigators and the ANZICS Clinical Trials Group. Continuous vs intermittent β-lactam antibiotic infusions in critically ill patients with sepsis: the BLING III randomized clinical trial. JAMA. 2024;332(8):629-637

SSSP-2

Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. JAMA. 2017;318(13):1233-1240

Trauma

PROPPR

Holcomb. Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma: The PROPPR Randomized Clinical Trial. JAMA 2015;313(5):471

PAMPer

Sperry. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med 2018; 379:315-326

PROCOAG

2000

Bouzat. Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion. The PROCOAG Randomized Clinical Trial. JAMA 2023;epublished March 21st

CRYOSTAT-2

Davenport. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury. The CRYOSTAT-2 Randomized Clinical Trial. JAMA 2023;epublished October 12th

Bickell

Bickell. Immediate versus delayed fluid resuscitaion for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331:1105-1109

PATCH-Trauma

The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group. Prehospital Tranexamic Acid for Severe Trauma. N Engl J Med 2023;389:127-136

CRASH-2

CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010;376:23-32

BEST-TRIP

Chesnut. A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury. New Engl J Med 2012;367:2471-2481

RESCUEicp

Hutchinson. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension (RESCUEicp). N Engl J Med 2016;375:1119-1130

HEMOTION

Turgeon. Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury. N Eng J Med 2024;391:722-735

Eurotherm3235

Andrews. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury (Eurotherm3235 Trial). N Engl J Med 2015;epublished October 7th

Endocrine

NICE-SUGAR

2000

NICE-SUGAR Study Investigators. Intensive versus Conventional Glucose Control in Critically Ill Patients. N Engl J Med 2009;360:1283-97.

VIOLET

2019

The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early High-Dose Vitamin D3 for Critically Ill, Vitamin D–Deficient Patients (VIOLET). N Engl J Med 2019; 381:2529-2540

VICTAS

Sevransky. Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis. The VICTAS Randomized Clinical Trial. JAMA 2021;325(8):742-750

Annane

Annane. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871

ADRENAL

Venkatesh. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL). N Engl J Med 2018;2018;378:797-808

APROCCHSS

Annane. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock (APROCCHSS). N Engl J Med 2018;378:809-818

Miscellaneous

TELESCOPE

Pereira. Effect of Tele-ICU on Clinical Outcomes of Critically Ill Patients. The TELESCOPE Randomized Clinical Trial. JAMA 2024;epublished October 9th

CHECKLIST-ICU

2013

BRICNet. Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients. A Randomized Clinical Trial (CHECKLIST-ICU). JAMA 2016;315(14):1480-1490

TEAM

The TEAM Study Investigators and the ANZICS Clinical Trials Group. Early Active Mobilization during Mechanical Ventilation in the ICU. N Engl J Med 2022; 387:1747-1758

Last updated January 27th, 2026