Combination Therapies to Reduce Carriage of SARS-Cov-2 and Improve Outcome of COVID-19 in Ivory Coast: a Phase Randomized IIb Trial
Keywords
Abstract
Dates
| Last Verified: | 06/30/2020 |
| First Submitted: | 07/05/2020 |
| Estimated Enrollment Submitted: | 07/08/2020 |
| First Posted: | 07/09/2020 |
| Last Update Submitted: | 07/08/2020 |
| Last Update Posted: | 07/09/2020 |
| Actual Study Start Date: | 07/19/2020 |
| Estimated Primary Completion Date: | 11/19/2020 |
| Estimated Study Completion Date: | 12/19/2020 |
Condition or disease
Intervention/treatment
Drug: Lopinavir/Ritonavir 200 MG-50 MG Oral Tablet
Drug: Lopinavir/ritonavir + telmisartan
Drug: Lopinavir/ritonavir + atorvastatin
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Active Comparator: Lopinavir/ritonavir Lopinavir boosted by ritonavir 200mg/50mg: 2 tablets morning and evening from Day 1 to Day 10 | |
| Experimental: Lopinavir/ritonavir + telmisartan Lopinavir boosted by ritonavir 200mg/50mg: 2 tablets morning and evening from Day 1 to Day 10
Telmisartan 40 mg : 1 tablet daily from Day 1 to Day 10 | Drug: Lopinavir/ritonavir + telmisartan 1 tablet daily from Day 1 to Day 10 |
| Experimental: Lopinavir/ritonavir + atorvastatin Lopinavir boosted by ritonavir 200mg/50mg: 2 tablets morning and evening from Day 1 to Day 10
Atorvastatin 20 mg : 1 tablet daily from Day 1 to Day 10 | Drug: Lopinavir/ritonavir + atorvastatin 1 tablet daily from Day 1 to Day 10 |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Patients over 18 years of age. - With SARS-CoV-2 infection confirmed by specific PCR. - With clinical manifestations of the infection, such as fever or cough, or otolaryngologic (ORL) signs or respiratory difficulties, that started less than 7 days ago. - COVID-19 specific treatment-naive. - Women of childbearing age should accept the use of mechanical contraception during the study period. - Informed consent signed by the patient. Exclusion Criteria: - Severe form of infection requiring oxygen therapy > 4l/min to achieve oxygen saturation > 94%. - Patient whose weight is < 35kg. - Pharmacological investigation contraindicating the introduction of a CYP450 inhibitor, in particular the CYP3A4 isoform. - Known hypersensitivity to lopinavir, ritonavir, telmisartan, atorvastatin or their excipients. - Renal impairment (eGFR <30 mL/min, CKD-EPI formulation). - Known cirrhosis. - Transaminases > 3N. - Bilirubin > 2.6N. - Electrocardiogram showing QTc> 500 ms. - HIV-infected patient without treatment or treated with protease inhibitors (lopinavir, darunavir, atazanavir). - Ongoing exposure to statins. - Contraindications to the use of statin: CPK > 5N, history of rhabdomyolysis or myopathies, increased risk when atorvastatin is administered with strong CYP3A4 inhibitors or transport proteins (cyclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole, letermovir, erythromycin, diltiazem, verapamil, fluconazole). - Ongoing exposure to sartans. - Contraindications to the use of telmisartan: patient on angiotensin-converting enzyme (ACE) inhibitors, aliskiren or other angiotensin receptor blockers (ARB). - Curatorship or guardianship. - Pregnancy or breastfeeding. - Dementia or any other condition that prevents informed consent. - Any reason that, at the discretion of the investigator, would compromise patient safety and cooperation in the trial. |
Outcome
Primary Outcome Measures
1. Proportion of patients with undetectable nasopharyngeal swab SARS-CoV-2 PCR and C-reactive protein (CRP) < 27 mg/L at Day 11 [Day 11]
Secondary Outcome Measures
1. Proportion of patients with clinical improvement on the 7-point ordinal scale at Day 11 and Day 28 [Day 11 and Day 28]
2. Kinetics of SARS-CoV-2 viral load [Up to Day 28]
3. Death rate at Day 11 and Day 28 [Day 11 and Day 28]
4. All causes of death and Acute respiratory distress syndrome (ARDS) at Day 28 [Day 28]
5. Time to hospital discharge [Up to Day 28]
6. Duration of oxygen supplementation [Up to Day 28]
7. Prevalence of grade III or IV adverse events [Up to Day 28]
8. Residual concentration of lopinavir, telmisartan and atorvastatin [Up to Day 28]
9. Evolution of inflammatory and immunological markers (CRP, fibrinogen, ferritin, d-dimer, dosing of IgG, IgA, IgM; TCD4, CD8, B lymphocytes, NK lymphocytes; naïve/memory T lymphocytes) [Up to Day 28]
10. Evolution of endothelial activation markers (VEGF and soluble VEGF receptor,VE-cadherin, PECAM/CD31, CD42 and angiopoietin-2) [Up to Day 28]
11. Proportion of patients with good results according to HIV status [Up to Day 28]
12. Number of contact cases infected by COVID-19 at Day 28 [Day 28]
