Atorvastatin and telmisartan do not reduce nasopharyngeal carriage of SARS-CoV-2 in mild or moderate COVID-19 in a phase IIb randomized controlled trial

Abstract

Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins. We implemented 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 / 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 ≥ 40 and C-reactive protein < 27 mg/L. 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 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. Among adults with mild to moderate COVID-19 infection, the addition of telmisartan or atorvastatin, to the standard LPVr treatment is not associated with a better virological or clinical outcome.Trial registration: NCT04466241, registered on 10/07/2020.

Keywords: Atorvastatin; Randomized controlled trial; SARS-CoV-2; Telmisartan.

Fig. 1

Trial flowchart (ANRS COV01 INTENSE-COV). ARBs: angiotensin II receptor blockers; LPVr: lopinavir/ritonavir; TLM: telmisartan; ATV: atorvastatin; ¹ These patients answered phone calls and said they would come to visits, but did not.

Fig. 2

Signs and symptoms of COVID-19 before baseline (ANRS COV01 INTENSE-COV). LPVr: lopinavir/ritovanir; TLM: telmisartan; ATV: atorvastatin.

Fig. 3

Evolution of Ct (panel A) and CRP (panel B): median and interquartile range (ANRS COV01 INTENSE-COV). LPVr: lopinavir/ritonavir; TLM: telmisartan; ATV: atorvastatin, Ct: SARS-CoV2 viral load (number of RT-PCR cycles); CRP: C-reactive protein.