Prevention and Early Treatment of Acute Lung Injury (PETAL) Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) - Catalog
Prevention and Early Treatment of Acute Lung Injury (PETAL) Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS)
HLB02792324a
PETAL-CLOVERS
PTC
False
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
True
True
Coded
https://petalnet.org/studies.html
False
Clinical Trial
Open BioLINCC Study
Adult
Drug: Early Vasopressors
Other: Early Fluids
2023-10-13
2023-10-13
2023-10-13
None
March 2018 - January 2023
DLD
Lung
non-HIV
non-COVID
None
None
No
No
Yes
No
Yes, For Some Specimens
Yes
Use of specimens in non-genetic research is unrestricted. Use of specimens in genetic research is tiered with respect to ARDS-related research and research related to other medical conditions. Specimens may not be used directly to produce commercial products.
Septic Shock
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.
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.
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.
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.
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.
Plasma
Whole Blood
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.
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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.
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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.