A recent study published in Scientific Reports investigated whether atorvastatin or telmisartan, when added to lopinavir/ritonavir (LPVr), could improve outcomes in patients with mild to moderate COVID-19. The multicenter, prospective, randomized controlled trial, named INTENSE-COV, found no significant benefit in reducing nasopharyngeal carriage of SARS-CoV-2 with the addition of either drug.
The trial, conducted across two designated COVID-19 facilities in Abidjan, Ivory Coast, enrolled adult patients with confirmed SARS-CoV-2 infection presenting with mild to moderate symptoms within seven days of onset. Participants were randomized to receive either LPVr alone, LPVr plus telmisartan (10 mg once daily), or LPVr plus atorvastatin (20 mg once daily) for 10 days. The primary endpoint was a composite of virological and inflammatory markers, defined as a cycle threshold (Ct) ≥ 40 on RT-PCR for SARS-CoV-2 and a C-reactive protein (CRP) level < 27 mg/L at day 11.
The study enrolled patients with mild to moderate COVID-19. Exclusion criteria included severe illness requiring high-flow oxygen, significant liver disease, myopathy, rhabdomyolysis, and known contraindications to statins or telmisartan. The primary outcome, viro-inflammatory success at day 11, was not significantly different between the three arms. The researchers defined viro-inflammatory success as achieving a Ct value of 40 or greater along with a CRP level below 27mg/L. This threshold was chosen based on local standards for viral load negativity and CRP's predictive value for severe COVID-19.
Detailed Findings
The results indicated that the addition of telmisartan or atorvastatin to LPVr did not significantly improve the primary endpoint of viro-inflammatory success at day 11. Specifically, the study aimed to detect a 50% improvement in viro-inflammatory success with the combination therapies compared to LPVr monotherapy, but this was not observed. The trial's statistical analysis included intention-to-treat and complete case analyses, with missing data imputed as failures. Sensitivity analyses using different Ct thresholds also yielded similar results.
Implications and Context
These findings contribute to the growing body of evidence evaluating potential treatments for COVID-19. While some studies have suggested potential benefits of statins and angiotensin receptor blockers (ARBs) in viral infections, this trial did not find evidence to support their use in reducing SARS-CoV-2 viral load or inflammation in early-stage COVID-19 when added to standard antiviral therapy. The study underscores the importance of conducting rigorous, randomized controlled trials to assess the efficacy of repurposed drugs for emerging infectious diseases.
Study Limitations
The authors acknowledge that changes in national recommendations during the trial led to missing primary endpoint data for some patients, which required post-hoc analysis. Additionally, the open-label design could have introduced bias. The study was conducted in Ivory Coast, and the generalizability of the findings to other populations may be limited.
