NCT04643691: COVIDANCE

Losartan and Spironolactone Treatment for ICU Patients With COVID-19 Suffering From ARDS

Terminated Phase 2 Last updated 24 June 2024

What this trial tests

Phase 2 trial testing Losartan 50 mg and Spironolactone 25 mg pillules oral use in COVID-19 in 78 participants. Terminated before completion.

Timeline

11 September 2020

Primary endpoint
7 December 2021

7 December 2021

Quick facts

Lead sponsor	Assistance Publique Hopitaux De Marseille
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	78
Start date	11 September 2020
Primary completion	7 December 2021
Estimated completion	7 December 2021
Sites	1 location across France

Drugs / interventions tested

• Losartan 50 mg and Spironolactone 25 mg pillules oral use — full drug profile →

Conditions studied

• COVID-19 — all drugs for COVID-19 →
• ARDS — all drugs for ARDS →

Sponsor

Assistance Publique Hopitaux De Marseille — full company profile →

Who can join

Adults 18 to 80, any sex, with COVID-19 or ARDS. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Coronavirus disease (COVID-19) is a current pandemic infection caused by an RNA virus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Severe forms of COVID-19 are most often responsible for isolated respiratory failure in the form of acute respiratory distress syndrome (ARDS), which accounts for most of the mortality. Angiotensin converting enzyme 2 (ACE2) has been shown to be a co-receptor for the entry of SARS-CoV-2 into cells and is likely to play a prolonged role in the pathogenesis of COVID-19. ACE2 and angiotensin (1-7) have been shown to be protective in a number of different lung lesion models. In a mouse model of acidic lung injury, negative regulation of ACE2 by COVID, the SARS virus responsible for the 2003 SARS outbreak, worsened the lung injury which was improved by treatment with ARBs.

We believe that blocking the first RAS pathway at the end of the chain on the AT1r angiotensin 2 receptor may prevent the initiation of this chain reaction and limit decompensation secondary to the disruption of the equilibrium of the renin-angiotensin system. We have several molecules that block the AT1r angiotensin-2 receptor (ARBs) as well as a molecule that blocks the secretion of aldosterone (spironolactone). The main objective is to demonstrate the value of losartan and spironolactone therapy in the regulation of the renin-angiotensin system in improving the prognosis of patients infected with COVID-19 and suffering from acute respiratory distress syndrome.

This is a prospective, multicenter, randomized, open-label, controlled, therapeutic trial studying two parallel groups. The population included in this study is any major patient in acute respiratory distress hospitalized in intensive care requiring oxygen support of at least 6L/min and suffering from a PCR-confirmed SARS-cov2 infection. The control group will benefit from the usual resuscitation management of COVID19 , and the experimental group will benefit from losartan and spironolactone treatment in addition to the usual management, according to the study protocol. The number of subjects required has been calculated and 45 patients for each group, for a total of 90 patients.

The SOFA score at D7 will be compared between the "experimental" versus "control" groups using a mean comparison method. The comparison of this criterion and all secondary criteria of judgments between the 2 groups will be performed using a Student or Mann-Whitney test based on the normality of the distribution. The significance threshold will be set at 0.05. No intermediate analysis is scheduled. The analysis will be blinded.

The main expected outcome is an improved prognosis with a decrease in the SOFA severity score at 7 days in resuscitation patients, resulting in an improvement in organ failure. The expected secondary results will be to show the interest of ARA2/Spironolactone treatment on oxygenation based on the PaO2/FiO2 ratio, mechanical ventilation duration and mortality.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cardiac involvement in the long-term implications of COVID-19.
   Satterfield BA, Bhatt DL, Gersh BJ. · · 2022 · cited 101× · PMID 34686843 · DOI 10.1038/s41569-021-00631-3
2. Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review.
   Hu S, Jiang S, Qi X, Bai R, et al · · 2022 · cited 68× · PMID 34762760 · DOI 10.1002/ddr.21895
3. The Role of Renin-Angiotensin-Aldosterone System in the Heart and Lung: Focus on COVID-19.
   Mascolo A, Scavone C, Rafaniello C, De Angelis A, et al · · 2021 · cited 34× · PMID 33959029 · DOI 10.3389/fphar.2021.667254
4. Neurological complications associated with Covid-19; molecular mechanisms and therapeutic approaches.
   Mahboubi Mehrabani M, Karvandi MS, Maafi P, Doroudian M. · · 2022 · cited 29× · PMID 35138001 · DOI 10.1002/rmv.2334
5. Beneficial Effects of Mineralocorticoid Receptor Pathway Blockade against Endothelial Inflammation Induced by SARS-CoV-2 Spike Protein.
   Jover E, Matilla L, Garaikoetxea M, Fernández-Celis A, et al · · 2021 · cited 21× · PMID 34204890 · DOI 10.3390/biomedicines9060639
6. COVID-19 and renin angiotensin aldosterone system: Pathogenesis and therapy.
   Babajani F, Kakavand A, Mohammadi H, Sharifi A, et al · · 2021 · cited 16× · PMID 34869917 · DOI 10.1002/hsr2.440
7. Roles of steroid receptors in the lung and COVID-19.
   Leach DA, Brooke GN, Bevan CL. · · 2021 · cited 11× · PMID 34328182 · DOI 10.1042/ebc20210005
8. Mineralocorticoid Receptor Antagonist (Potassium Canrenoate) Does Not Influence Outcome in the Treatment of COVID-19-Associated Pneumonia and Fibrosis-A Randomized Placebo Controlled Clinical Trial.
   Kotfis K, Karolak I, Lechowicz K, Zegan-Barańska M, et al · · 2022 · cited 4× · PMID 35215312 · DOI 10.3390/ph15020200