Prevention and Early Treatment of Acute Lung Injury (PETAL) Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) - Catalog

Name

Prevention and Early Treatment of Acute Lung Injury (PETAL) Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS)

Accession Number

HLB02792324a

Acronym

PETAL-CLOVERS

Related studies

BSI Study IDs

PTC

Is public use dataset

False

Keywords

Fluid management

Sepsis-induced hypotension

vasopressors

Infections

Systemic Inflammatory Response Syndrome

Inflammation

Pathologic Processes

Sepsis

Adrenergic alpha-Agonists

Adrenergic Agents

Neurotransmitter Agents

Molecular Mechanisms of Pharmacological Action

Physiological Effects of Drugs

Sympathomimetics

Autonomic Agents

Peripheral Nervous System Agents

Norepinephrine

Vasoconstrictor Agents

Has Study Datasets

True

Has Specimens

True

Specimen ID Type

Coded

Study Website

https://petalnet.org/studies.html

The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.

False

Study type

Clinical Trial

Collection Type

Open BioLINCC Study

Cohort type

Adult

Interventions

Drug: Early Vasopressors

Other: Early Fluids

Study Open Date (Data)

2023-10-13

Study Open Date (Specimens)

2023-10-13

Date materials available

2023-10-13

Last updated

None

Study period

March 2018 - January 2023

Study Contacts
NHLBI Division

DLD

Classification

Lung

HIV study classification

non-HIV

COVID study classification

non-COVID

Pre-Website # of Specimens Shipped

None

# of Returned Specimens

None

Conditions

Septic Shock

Objectives

To compare the effects of a restrictive fluid strategy (with early use of vasopressors) to a liberal fluid strategy in patients with sepsis-induced hypotension.

Background

Intravenous fluid resuscitation is a common therapy used in the initial treatment of patients with septic shock and sepsis-induced hypotension. The goal of initial fluid therapy is to increase depleted or functionally reduced intravascular volume that occurs in sepsis due to a vasodilated vascular network. However, intravenous fluid resuscitation can create dilutional coagulopathy, fluid overload, and pathogenic edema in the lungs and other organs. Vasopressor agents are also commonly used to treat hypoperfusion by inducing constriction of arterioles and venules and increasing cardiac contractility. Vasopressor therapy also comes with risks that include vasoconstriction resulting in tissue ischemia, increased cardiac workload, and arrhythmias. Clinicians have used these strategies, typically in combination, to provide supportive care for patients with sepsis-induced hypoperfusion. However, at the time of the CLOVERS study, there was limited data to guide specific use of these therapies, including fluid volumes, in the early care of patients with sepsis-induced hypotension. The CLOVERS study hypothesized that a restrictive fluid strategy used during the first 24-hours of resuscitation for sepsis-induced hypotension would lead to lower mortality before discharge home by day 90 than a liberal fluid strategy.

Participants

Adult patients (>18 years of age) with a suspected or confirmed infection (broadly defined as the administration or planned administration of antibiotic agents) and sepsis-induced hypotension (systolic blood pressure, <100 mm Hg after the administration of ≥1000 ml of intravenous fluid) were eligible. Key exclusion criteria were an elapse of more than 4 hours since the meeting of the criteria for hypotension refractory to the intravenous administration of at least 1000 ml of fluid, an elapse of more than 24 hours since presentation at the hospital, previous receipt of more than 3000 ml of intravenous fluid during this episode (including prehospital administration of fluid by emergency medical services), the presence of fluid overload, and severe volume depletion from non-sepsis causes.


A total of 1563 patients, from 60 medical centers, of the planned 2,230 participants were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Enrollment in the trial was ended after the second interim analysis due to a lack of significant difference observed between the two 24-hour strategies.

Design

This study was a multi-center, prospective, phase 3 randomized non-blinded interventional trial of fluid treatment strategies in the first 24 hours for patients with sepsis-induced hypotension. Participants were randomly assigned in a 1:1 ratio to either a restrictive fluid strategy (with early vasopressor use) or a liberal fluid strategy. In each group, the assigned protocol was followed for a period of 24 hours. The restrictive fluid protocol prioritized vasopressors as the primary treatment for sepsis-induced hypotension, with “rescue fluids” being permitted for prespecified indications that suggested severe intravascular volume depletion. The liberal fluid protocol consisted of a recommended initial 2000-ml intravenous infusion of isotonic crystalloid, followed by fluid boluses administered on the basis of clinical triggers (e.g., tachycardia) with “rescue vasopressors” permitted for prespecified indications. A protocol amendment implemented in October 2019 allowed for limiting the initial infusion to 1000 ml if the patient’s blood pressure and heart rate had stabilized and the clinical assessment was that the patient was unlikely to benefit from additional intravenous fluid administration. The clinical team could override the protocol-specified care instructions at any time if it was judged to be in the best interest of the patient.


The primary outcome was death from any cause before discharge home by day 90. Secondary outcomes included 28-day measures of the number of days free from ventilator use, days free from renal-replacement therapy, days free from vasopressor use, days out of the ICU, and days out of the hospital.

Conclusions

Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality, or other measures of recovery such as length of hospital stay, before discharge home by day 90 than the liberal fluid strategy.


National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network; Shapiro NI, Douglas IS, Brower RG, Brown SM, Exline MC, Ginde AA, Gong MN, Grissom CK, Hayden D, Hough CL, Huang W, Iwashyna TJ, Jones AE, Khan A, Lai P, Liu KD, Miller CD, Oldmixon K, Park PK, Rice TW, Ringwood N, Semler MW, Steingrub JS, Talmor D, Thompson BT, Yealy DM, Self WH. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. N Engl J Med. 2023 Feb 9;388(6):499-510. doi: 10.1056/NEJMoa2212663. Epub 2023 Jan 21. PMID: 36688507.

Disease classification

Publications

Mat types

Plasma
Whole Blood

Network

Prevention and Early Treatment of Acute Lung Injury (PETAL)

The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.

  • Subjects

    There are 1,563 total subjects: 781 Liberal Fluid Group, 782 Restrictive Fluid Group


    Last Modified: Feb. 7, 2024, 10:12 a.m.
  • Age

     

    Liberal Fluid Group

    Restrictive Fluid Group

    Total Subjects

    18-29

    35

    33

    68

    30-39

    69

    72

    141

    40-49

    83

    97

    180

    50-59

    163

    174

    337

    60-69

    206

    200

    406

    70-79

    151

    124

    275

    80-89

    74

    82

    156


    Last Modified: Feb. 7, 2024, 10:13 a.m.
  • Sex

     

    Liberal Fluid Group

    Restrictive Fluid Group

    Total Subjects

    Female

    366

    371

    737

    Male

    415

    411

    826


    Last Modified: Feb. 7, 2024, 10:12 a.m.
  • Race

     

    Liberal Fluid Group

    Restrictive Fluid Group

    Total Subjects

    Asian

    26

    27

    53

    Black or African-American

    112

    134

    246

    Not Reported

    67

    78

    145

    Unknown/Multiple

    5

    11

    16

    White

    571

    532

    1,103


    Last Modified: Feb. 7, 2024, 10:12 a.m.

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3.0 of the BioLINCC Handbook describes the components of the review process.

  • Material Types

    Plasma, Whole blood for DNA extraction, Whole blood for RNA extraction


    Last Modified: Jan. 25, 2024, 8:02 a.m.
  • General Freeze/Thaw Status

    Plasma and whole blood are unthawed.


    Last Modified: Jan. 29, 2024, 11:51 a.m.
  • Visits (Vials)

    11/04/2024

     

    Plasma

    Whole Blood, DNA Extraction

    Whole Blood, RNA Extraction

    DNA

    Total Vials

    Baseline

    5,450

    10,513

    1,293

    4,379

    21,635

    24 Hour

    6,316

    1,479

    1,142

    194

    9,131

    72 Hour

    4,687

    847

    828

    19

    6,381


    Last Modified: Nov. 4, 2024, 8:56 a.m.
  • Visits (Subjects)

    11/04/2024

     

    Plasma

    Total number of subjects

    Average volume (mL) per subject

    Baseline

    1,363

    2.99

    24 Hour

    1,218

    3.98

    72 Hour

    878

    4.04

     

     

    Whole Blood, DNA Extraction

    Total number of subjects

    Average volume (mL) per subject

    Baseline

    1,283

    4.09

    24 Hour

    1,145

    4.29

    72 Hour

    826

    4.22

     

     

    Whole Blood, RNA Extraction

    Total number of subjects

    Average volume (mL) per subject

    Baseline

    1,293

    6.90

    24 Hour

    1,142

    6.85

    72 Hour

    828

    6.83

     

     

    DNA

    Total number of subjects

    Average mass (ug) per subject

    Baseline

    1,229

    8.51

    24 Hour

    50

    5.68

    72 Hour

    3

    9.21


    Last Modified: Nov. 4, 2024, 8:56 a.m.