Combination Therapies to Reduce Carriage of SARS-Cov-2 and Improve Outcome of COVID-19 in Ivory Coast: a Phase Randomized IIb Trial

NCT04466241 | Completed Phase 2 DMC

• 1 other identifier: ANRS COV01 INTENSE COV
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 2

Brief Summary

In January 2020, the new SARS-CoV-2 coronavirus was identified in China. The disease caused by this coronavirus was named COVID-19 by the World Health Organization (WHO). Since March 11, 2020, the WHO has described the global situation of COVID-19 as a pandemic. In Côte d'Ivoire, as in other African countries, the number of cases is increasing exponentially. Coronaviruses are a family of viruses that cause illnesses ranging from the common cold to more severe pathologies. COVID-19 can result in fever or a feeling of fever (chills, hot-cold), cough, headache, aches and pains, unusual tiredness, sudden loss of smell, total disappearance of taste, or diarrhea. In severe forms, respiratory difficulties can lead to hospitalization in intensive care or even death. Numerous studies are currently being conducted around the world to seek effective treatment, but few of them have started specifically in Africa. Moreover, most of these studies are using a single drug to control the infection, whether these are repositioned drugs, i.e. already being used for other diseases, or other newer drugs. Currently in Côte d'Ivoire, the preferred treatment for COVID-19 is an antiviral: lopinavir/ritonavir (LPV/r), usually directed against the Human Immunodeficiency Virus (HIV). Since the number of viruses (viral load) is high in the respiratory tract during COVID-19 infection, we propose in INTENSE-COV (ICOV) clinical trial to study whether the combination of two drugs is more effective than taking a single drug on reducing the viral load in the respiratory tract but also on reducing inflammation. These drugs include the LPV/r already in use in Côte d'Ivoire as well as an antihypertensive drug - telmisartan, and a drug that lowers blood cholesterol - atorvastatin. All three have been known for a long time and have been shown to be effective against other viruses. In addition, they are generic, inexpensive and readily available in all countries. The objectives of the ICOV study are therefore to improve viral eradication from the patient's body and respiratory tract, to reduce inflammation, to improve more rapidly the patient's state of health and to reduce the risk of transmission of the virus to others. To participate in ICOV, patients must be over 18 years of age, have a COVID-19 infection confirmed by a specific test, have clinical manifestations of the infection, and have signed an informed consent. They will then be randomized into 3 treatment groups to ensure the robustness of the study results. The reference group will be treated with LPV/r, according to current recommendations in Côte d'Ivoire. The other 2 groups will be treated with LPV/r + telmisartan and LPV/r + atorvastatin respectively. The treatment will last 10 days and patients will be followed for a total of 28 days.

Conditions

COVID-19; COVID-19 Drug Treatment; Severe Acute Respiratory Syndrome Coronavirus 2

Keywords

COVID-19; Combination therapy; Atorvastatin; Telmisartan; Lopinavir/ritonavir; SARS-COV-2; Viral load

Outcome Measures

Primary Outcomes (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 Outcomes (12)

• Proportion of patients with clinical improvement on the 7-point ordinal scale at Day 11 and Day 28

  Day 11 and Day 28

• Kinetics of SARS-CoV-2 viral load

  Up to Day 28

• Death rate at Day 11 and Day 28

  Day 11 and Day 28

• All causes of death and Acute respiratory distress syndrome (ARDS) at Day 28

  Day 28

• Time to hospital discharge

  Up to Day 28

Study Arms (3)

Lopinavir/ritonavir

ACTIVE COMPARATOR

Lopinavir boosted by ritonavir 200mg/50mg: 2 tablets morning and evening from Day 1 to Day 10

Drug: Lopinavir/Ritonavir 200 MG-50 MG Oral Tablet

Lopinavir/ritonavir + telmisartan

EXPERIMENTAL

* 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 200 MG-50 MG Oral Tablet; Drug: Telmisartan 40Mg Oral Tablet

Lopinavir/ritonavir + atorvastatin

EXPERIMENTAL

* 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 200 MG-50 MG Oral Tablet; Drug: Atorvastatin 20 Mg Oral Tablet

Interventions

Lopinavir/Ritonavir 200 MG-50 MG Oral Tablet DRUG

2 tablets morning and evening from Day 1 to Day 10

Also known as: LPV/r, Aluvia

Lopinavir/ritonavir; Lopinavir/ritonavir + atorvastatin; Lopinavir/ritonavir + telmisartan

Telmisartan 40Mg Oral Tablet DRUG

1 tablet daily from Day 1 to Day 10

Also known as: TMS, Micardis, Pritor

Lopinavir/ritonavir + telmisartan

Atorvastatin 20 Mg Oral Tablet DRUG

1 tablet daily from Day 1 to Day 10

Also known as: ATV, Tahor

Lopinavir/ritonavir + atorvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• University of Bordeaux: collaborator
• PACCI Program: collaborator

Study Sites (2)

Service des Maladies Infectieuses et Tropicales, Centre Hospitalier et Universitaire (CHU) Treichville

Abidjan, 01 BP V3, Côte d’Ivoire

Location

Centre de Traitement des Maladies Infectieuses (CTMI), CHU de Yopougon

Abidjan, 21 BP 632, Côte d’Ivoire

Location

Related Publications (1)

• Bonnet F, Doumbia A, Machault V, Ello FN, Bellecave P, Akpovo CB, Sidibe BT, Fernandez L, Kouame A, Adjogoua E, Dosso M, Niangoran S, Journot V, Eholie SP. 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. Sci Rep. 2024 Oct 23;14(1):25028. doi: 10.1038/s41598-024-72449-1.

  PMID: 39443527 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Lopinavir; Ritonavir; lopinavir-ritonavir drug combination; Telmisartan; Atorvastatin; Tablets

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrroles; Heptanoic Acids; Fatty Acids; Lipids; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Phase IIb, comparative, multicenter, randomized, superiority, parallel-group, open-label clinical trial

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 10, 2020
• Study Start: November 27, 2020
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: December 27, 2024

Record last verified: 2024-12

Locations

CÔ (2)