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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
More...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: Suggested Citation