ArticleEClinicalMedicine2021
Seven days treatment with the angiotensin II type 2 receptor agonist C21 in hospitalized COVID-19 patients; a placebo-controlled randomised multi-centre double-blind phase 2 trial.
Article in EClinicalMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04452435 (A Randomised, Double-blind, Placebo-controlled, Phase 2 Trial Investigating the Safety and Efficacy of C21 in Hospitalised Subjects With COVID-19 Infection Not Requiring Mechanical Ventilation), which is not on this map. Cited by 23 papers, 2 of them syntheses that pooled it.
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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.
A Randomised, Double-blind, Placebo-controlled, Phase 2 Trial Investigating the Safety and Efficacy of C21 in Hospitalised Subjects With COVID-19 Infection Not Requiring Mechanical Ventilation
Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles: A Systematic Review.JAMA network open · 2023Pooled it
- Pooled it
- Trial
- Beneficial effects of the ATERJ open research · 2026Article
- The balance between classical and alternative renin-angiotensin system in ARDS: a narrative review.Journal of intensive care · 2026Review
- The angiotensin II type 2 receptor attenuates aging-associated arterial stiffness in female mice.American journal of physiology. Heart and circulatory physiology · 2025Article
- The novel AT2 receptor ligand, β-Pro7 Ang III, induces equivalent anti-fibrotic effects to Compound 21 but broader anti-fibrotic effects than pirfenidone in mice with bleomycin-induced pulmonary fibrosis.Clinical science (London, England : 1979) · 2025Article
- The circulating renin-angiotensin system and mortality among patients hospitalized for COVID-19: a mechanistic substudy of the ACTIV-4 Host Tissue trials.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Microvascular angiotensin II type 2 receptor function is enhanced in young females and declines in a model of murine aging.The journal of cardiovascular aging · 2024Article
- Alternative Renin-Angiotensin System.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial.EClinicalMedicine · 2024Article
- Angiotensin II type 2 receptor agonist attenuates LPS-induced acute lung injury through modulating THP-1-derived macrophage reprogramming.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Perspectives on Post-COVID-19 Pulmonary Fibrosis Treatment.Journal of personalized medicine · 2023Review
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment.Circulation research · 2023Review
- Article
- Effects of the Oral Angiotensin II Type 2 Receptor Agonist C21 in Sugen-Hypoxia Induced Pulmonary Hypertension in Rats.International journal of molecular sciences · 2023Article
- Article
- Coronavirus disease 2019 and acute cerebrovascular events: a comprehensive overview.Frontiers in neurology · 2023Review
- The Angiotensin ATPharmacological reviews · 2022Review
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCOVID-19 morbidity and mortality remains high and the need for safe and effective drugs continues despite vaccines.
methodsDouble-blind, placebo-controlled, multi-centre, randomised, parallel group phase 2 trial to evaluate safety and efficacy of oral angiotensin II type 2 receptor agonist C21 in hospitalized patients with COVID-19 and CRP ≥ 50-150 mg/L conducted at eight sites in India (NCT04452435). Patients were randomly assigned 100 mg C21 bid or placebo for 7 days in addition to standard of care. Primary endpoint: reduction in CRP. The study period was 21 July to 13 October 2020.
findings106 patients were randomised and included in the analysis (51 C21, 55 placebo). There was no significant group difference in reduction of CRP, 81% and 78% in the C21 and placebo groups, respectively, with a treatment effect ratio of 0.85 [90% CI 0.57, 1.26]. In a secondary analysis in patients requiring supplemental oxygen at randomisation, CRP was reduced in the C21 group compared to placebo. At the end of the 7-day treatment, 37 (72.5%) and 30 (54.5%) of the patients did not require supplemental oxygen in the C21 and placebo group, respectively (OR 2.20 [90% CI 1.12, 4.41]). A post hoc analysis showed that at day 14, the proportion of patients not requiring supplemental oxygen was 98% and 80% in the C21 group compared to placebo (OR 12.5 [90% CI 2.9, 126]). Fewer patients required mechanical ventilation (one C21 patient; four placebo patients), and C21 was associated with a numerical reduction in the mortality rate (one vs three in the C21 and placebo group, respectively). Treatment with C21 was safe and well tolerated.
interpretationAmong hospitalised patients with COVID-19 receiving C21 for 7 days there was no reduction in CRP compared to placebo. However, a post-hoc analysis indicated a marked reduction of requirement for oxygen at day 14. The day 14 results from this study justify further evaluation in a Phase 3 study and such a trial is currently underway.
fundingVicore Pharma AB and LifeArc, UK.
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