Mechanistic Assessment of Norepinephrine Therapy vs. Angiotensin-II in Septic Shock
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Angiotensin II, Norepinephrine.
- Who it may be relevant to
- Registry conditions: Septic Shock. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Mechanistic Assessment of Norepinephrine TheRapy vs. Angiotensin-II in Septic Shock (MANTRA) Grant Submission- Dysfunctional Renin-Angiotensin System in Septic Shock
Overview
Despite best therapy efforts, sepsis and septic shock are associated with mortality rates of up to 40%. This clinical trial will determine the benefit of exogenous Angiotensin II versus norepinephrine (conventional care) treatment in septic shock patients. This trial will determine whether there are better predictors of septic shock severity. This approach may inform more appropriate treatment regimens and improve outcomes for these patients.
Detailed description
This study will determine whether normalization of renin-angiotensin-aldosterone system (RAAS) signaling in sepsis occurs more rapidly with treatment with Angiotensin II compared with conventional vasopressors. Trial samples will be used to identify the best RAAS biomarker predictor of treatment response via in-depth longitudinal analysis of RAAS component and to determine the extent and mechanisms of Angiotensin II impact on innate immune function during sepsis. Successful accomplishment of our aims will provide the capability to improve endotyping of septic patients by establishing the most precise and robust measurement of renin (and RAAS dysfunction). This work will improve staging and clinical precision and will facilitate the criteria for therapeutic development of targets in septic shock.
Interventions
- Drug Angiotensin II
randomized to receive Angiotensin II continuous infusion for up to 48 hours - Drug Norepinephrine
randomized to receive Norepinephrine continuous infusion for up to 48 hours
Primary outcome measures
- Mean Renin Level - Hour 24 [Time frame: Hour 24]
Secondary outcome measures (12)
- Norepinephrine Equivalent Dose Requirement (NEE) [Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72]
- Number of Days Without Renal Replacement Therapy [Time frame: Day 28]
- Number of Days of Vasopressor Use [Time frame: Day 28]
- Number of Days Without Mechanical Ventilation [Time frame: Day 28]
- Number of Hours Vasopressor Free [Time frame: Hour 72]
- Number of Hours Alive [Time frame: Hour 72]
- Number of Days Alive [Time frame: Day 28]
- Mean Renin Level [Time frame: Baseline, Hour 3, Hour 12, Hour 48, Hour 72]
- Sequential Organ Failure Assessment (SOFA) Score [Time frame: Baseline, Hour 24, Hour 48]
- APACHE-II Score [Time frame: Baseline, Hour 24, Hour 48]
- Lactate Level [Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72]
- Kidney Disease Improving Global Outcomes (KDIGO) Stage [Time frame: Baseline, Hour 24, Hour 48]
Eligibility criteria
Inclusion criteria
\- The presence of septic shock, defined by sepsis-3 criteria: 1-adult patients (18 years or older) with septic shock, defined by SEPSIS-3 criteria: a) suspected or known infection, b) hypotension requiring vasopressors, and c) lactate >2mmol/L 2-receiving either norepinephrine or phenylephrine with or without additional vasopressor support 3- total norepinephrine equivalent dose (NED) ≥0.1 mcg/kg/min and ≤0.5 mcg/kg/min, to maintain a MAP of at least 65 mmHg, is required for randomization 4-ability to consent and randomize within 24 hrs of first reaching NED threshold and within 48 hrs of hospital arrival
Exclusion criteria
- Age <18 years
- Prisoners
- Pregnant women
- Patients for whom urgent surgery is anticipated
- Leukocyte count <1,000 cells/μL
- Absolute monocyte count <200 cells/μL
- Bone marrow transplant within the past 30 days
- Patients that will be withdrawing aggressive resuscitation, including withdraw of vasopressor support
- transfer from outside ICU
- history of liver cirrhosis with Child-Pugh score ≥6
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 2 centers
- Massachusetts General Hospital-Harvard — Boston
- Atrium Health Wake Forest Baptist — Winston-Salem
Identifiers
NCT: NCT06746753 · IRB00115287 · R01HL177834