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Therapeutic Combinations in Mild or Moderate COVID-19 to Reduce Nasopharyngeal Carriage of SARS-CoV-2 and Prevent Severe COVID-19 in Côte D’Ivoire: A Pragmatic Phase IIb Randomized Controlled Clinical Trial. The ANRS COV01 INTENSE-COV Trial

26 Pages Posted: 10 Oct 2022

See all articles by Fabrice Bonnet

Fabrice Bonnet

University of Bordeaux - Bordeaux Population Health Centre

Adama Doumbia

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie

Vanessa Machault

University of Bordeaux - Bordeaux Population Health Centre

Frederic Ello

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie

Pantxika Bellecave

University of Bordeaux - CHU de Bordeaux

Corinne Akpovo

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie

Baba Sidibe

University Hospital of Treichville - Service des Maladies Infectieuses et Tropicales

Laura Fernandez

University Hospital of Treichville

Antoine Koume

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie

Edgard Adjogoua

Institut Pasteur in Ivory Coast

Dosso Mireille

Institut Pasteur in Ivory Coast

Serge Niangoran

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie

Valerie Journot

University of Bordeaux - Bordeaux Population Health Centre

Serge Paul Eholié

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie

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Abstract

Background: Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins.

Methods: This was a randomized controlled tree-arm open label trial evaluating the benefits of adding telmisartan (TLM) or atorvastatin (ATV) to lopinavir boosted ritonavir (LPVr) on the SARS-CoV-2 nasopharyngeal viral load in patients with mild to moderate COVID-19 infection in Côte d’Ivoire. RT-PCR positive COVID-19 patients ≥18 years, with general or respiratory symptoms for less than 7 days were randomized (1:1:1) to receive LPVr (400 mg/100 mg twice daily), LPVr+TLM (10 mg once daily) or LPVr+ATV (20 mg once daily) for 10 days. The primary endpoint was viro-inflammatory success defined as a composite variable at day 11: Ct ³40 and C-reactive protein (CRP) <27 mg/L (NCT04466241).

Findings: We randomized 294 patients: 96 to LPVr, 100 to LPVr+TLM, 98 to LPVr+ATV arms. Baseline characteristics were well balanced between arms. In the primary analysis (missing = failure), 46% patients in the LPVr arm reached viro-inflammatory success at day 11 vs 43% in the LPVr+TLM arm (p=0.69) and 43% in the LPVr + ATV arm (p=0.68). The median time from baseline to complete resolution of COVID-19 related symptoms was not different between arms. Nine patients were hospitalized: 2 in the LPVr arm, 5 in the LPVr+TLM arm and 2 in the LPVr+ATV arm and 4 patients died, without relation to trial treatment.

Interpretation: Among adults with mild to moderate COVID-19 infection, the addition of telmisartan or atorvastatin, to the standard lopinavir/ritonavir treatment is not associated with a better virological or clinical outcome.

Trial Registration: The trial was registered on clinicaltrial.gov (NCT04466241, registered on July 10, 2020)

Funding: ANRS | Emerging Infectious Diseases

Declaration of Interest: Fabrice Bonnet has received consulting honoraria, research grants, or both from Gilead Sciences, MSD, and ViiV Healthcare, outside the submitted work. Other authors have nothing to disclose.

Ethical Approval: The trial was approved by the institutional national ethics committee (Comité National d’Ethique de la Vie et de la Santé (CNEVS), July 27, 2020)

Keywords: COVID-19, therapeutic trial, telmisartan, atorvastatin, lopinavir

Suggested Citation

Bonnet, Fabrice and Doumbia, Adama and Machault, Vanessa and Ello, Frederic and Bellecave, Pantxika and Akpovo, Corinne and Sidibe, Baba and Fernandez, Laura and Koume, Antoine and Adjogoua, Edgard and Mireille, Dosso and Niangoran, Serge and Journot, Valerie and Eholié, Serge Paul, Therapeutic Combinations in Mild or Moderate COVID-19 to Reduce Nasopharyngeal Carriage of SARS-CoV-2 and Prevent Severe COVID-19 in Côte D’Ivoire: A Pragmatic Phase IIb Randomized Controlled Clinical Trial. The ANRS COV01 INTENSE-COV Trial. Available at SSRN: https://ssrn.com/abstract=4243701 or http://dx.doi.org/10.2139/ssrn.4243701

Fabrice Bonnet (Contact Author)

University of Bordeaux - Bordeaux Population Health Centre ( email )

Adama Doumbia

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie ( email )

Vanessa Machault

University of Bordeaux - Bordeaux Population Health Centre ( email )

Frederic Ello

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie ( email )

Pantxika Bellecave

University of Bordeaux - CHU de Bordeaux ( email )

Bordeaux
France

Corinne Akpovo

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie ( email )

Baba Sidibe

University Hospital of Treichville - Service des Maladies Infectieuses et Tropicales ( email )

Laura Fernandez

University Hospital of Treichville ( email )

Antoine Koume

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie ( email )

Edgard Adjogoua

Institut Pasteur in Ivory Coast ( email )

Dosso Mireille

Institut Pasteur in Ivory Coast ( email )

Serge Niangoran

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie ( email )

Valerie Journot

University of Bordeaux - Bordeaux Population Health Centre ( email )

Serge Paul Eholié

Universite Félix Houphouet Boigny - University of Felix Houphouet Boigny - Unité Pédagogique de Dermatologie et Infectiologie ( email )