ArticleAnnals of intensive care2024
Angiotensin-(1-7) infusion in COVID-19 patients admitted to the ICU: a seamless phase 1-2 randomized clinical trial.
Article in Annals of intensive care, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04633772 (Randomized Clinical Trial Phase I/II for the Use of Angiotensin-), which is not on this map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized Clinical Trial Phase I/II for the Use of Angiotensin-(1-7) in the Treatment of Severe Infection by Sars-CoV-2
Who cites it
8 citing papers in PubMed.
- The balance between classical and alternative renin-angiotensin system in ARDS: a narrative review.Journal of intensive care · 2026Review
- Renin-angiotensin system activation and oxidative stress in hospitalized COVID-19 patients: a single-centre prospective observational study.Intensive care medicine experimental · 2026Article
- Angiotensin-(1-7) in asthma and pulmonary fibrosis: mechanisms of action, clinical safety, and nano-delivery strategies.Frontiers in pharmacology · 2026Review
- Nitric Oxide at the Nexus of ACE2 Biology and COVID-19: Implications for Cardiovascular and Neurodegenerative Comorbidities.Physiological research · 2025Review
- Unlocking Novel Therapeutic Potential of Angiotensin II Receptor Blockers.International journal of molecular sciences · 2025Review
- Renin-angiotensin-aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study.Annals of intensive care · 2025Article
- Interaction of SARS-CoV-2 and SARS-CoV-2 vaccines with renin angiotensin aldosterone system, clinical outcomes, and angiotensin (1-7) as a physiological treatment recommendation: hypothesis and theory article.Frontiers in medicine · 2025Article
- Intranasal liposomal angiotensin-(1-7) administration reduces inflammation and viral load in the lungs during SARS-CoV-2 infection in K18-hACE2 transgenic mice.Antimicrobial agents and chemotherapy · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
backgroundThe coronavirus-related disease (COVID-19) is mainly characterized by a respiratory involvement. The renin-angiotensin system (RAS) has a relevant role in the pathogenesis of COVID-19, as the virus enters host's cells via the angiotensin-converting enzyme 2 (ACE2).
methodsThis investigator-initiated, seamless phase 1-2 randomized clinical trial was conceived to test the safety and efficacy of continuous short-term (up to 7 days) intravenous administration of Angiotensin-(1-7) in COVID-19 patients admitted to two intensive care units (ICU). In addition to standard of care, intravenous administration of Angiotensin-(1-7) was started at 5 mcg/Kg day and increased to 10 mcg/Kg day after 24 h (Phase 1; open label trial) or given at 10 mcg/Kg day and continued for a maximum of 7 days or until ICU discharge (Phase 2; double-blind randomized controlled trial). The rate of serious adverse events (SAEs) served as the primary outcome of the study for Phase 1, and the number of oxygen free days (OFDs) by day 28 for Phase 2.
resultsBetween August 2020 and July 2021, when the study was prematurely stopped due to low recruitment rate, 28 patients were included in Phase 1 and 79 patients in Phase 2. Of those, 78 were included in the intention to treat analysis, and the primary outcome was available for 77 patients. During Phase 1, one SAE (i.e., bradycardia) was considered possibly related to the infusion, justifying its discontinuation. In Phase 2, OFDs did not differ between groups (median 19 [0-21] vs. 14 [0-18] days; p = 0.15). When patients from both phases were analyzed in a pooled intention to treat approach (Phase 1-2 trial), OFDs were significantly higher in treated patients, when compared to controls (19 [0-21] vs. 14 [0-18] days; absolute difference -5 days, 95% CI [0-7] p = 0.04).
conclusionsThe main findings of our study indicate that continuous intravenous infusion of Angiotensin-(1-7) at 10 mcg/Kg day in COVID-19 patients admitted to the ICU with severe pneumonia is safe. In Phase II intention to treat analysis, there was no significant difference in OFD between groups. Trial Registration ClinicalTrials.gov Identifier: NCT04633772-Registro Brasileiro de Ensaios Clínicos, UTN number: U1111-1255-7167.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.