Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
Trial no.: PACTR202007720062393 Date of Approval: 13/07/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Combination Therapies to Reduce Carriage of SARS-Cov-2 and Improve Outcome of COVID-19 in Ivory Coast: a Phase Randomized IIb Trial (INTENSE-COV)
Official scientific title Combination Therapies to Reduce the Nasopharyngeal Carriage of SARS-CoV-2 and Improve the Outcome of COVID-19 Infection in Ivory Coast (INTENSE-COV): a Phase IIb Randomized Clinical Trial
Brief summary describing the background and objectives of the trial In January 2020, the new SARS-CoV-2 coronavirus was identified in China. 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. Numerous studies are currently being conducted 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 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 HIV. Since the 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 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. Adult patients participating to ICOV will be randomized into 3 treatment groups. 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.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) INTENSE COV
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Treatment: Drugs
Anticipated trial start date 20/07/2020
Actual trial start date
Anticipated date of last follow up 20/10/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 294
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
ANRS COV01 Inserm-ANRS
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Lopinavir ritonavir 10 days Lopinavir boosted by ritonavir 200mg/50mg: 2 tablets morning and evening from Day 1 to Day 10 98 Active-Treatment of Control Group
Experimental Group Lopinavir ritonavir and telmisartan 10 days - 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 98
Experimental Group Lopinavir ritonavir and atorvastatin 10 days - 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 98
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- 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. - 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. 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 03/07/2020 Comite national dEthique des Sciences de la Vie et e la Sante
Ethics Committee Address
Street address City Postal code Country
Institut Pasteur de Cocody Abidjan 00000 Cote Divoire
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 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 Proportion of patients with clinical improvement on the 7-point ordinal scale at Day 11 Day 11
Secondary Outcome Kinetics of SARS-CoV-2 viral load Up to Day 28
Secondary Outcome Death rate at Day 11 and Day 28 Day 11 and Day 28
Secondary Outcome All causes of death and Acute respiratory distress syndrome (ARDS) at Day 28 Day 28
Secondary Outcome Time to hospital discharge Up to Day 28
Secondary Outcome Duration of oxygen supplementation Up to Day 28
Secondary Outcome Prevalence of grade III or IV adverse events Up to Day 28
Secondary Outcome Residual concentration of lopinavir, telmisartan and atorvastatin Up to Day 28
Secondary Outcome Evolution of inflammatory and immunological markers Up to Day 28
Secondary Outcome Evolution of endothelial activation markers Up to Day 28
Secondary Outcome Absence of symptoms at Day 28 Day 28
Secondary Outcome Proportion of patients with good results according to HIV status Up to Day 28
Secondary Outcome Number of contact cases infected by COVID-19 at Day 28 Day 28
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
SMIT CHU de Treichville Treichville Abidjan Cote Divoire
CTMI CHU de Yopougon Yopougon Abidjan Cote Divoire
FUNDING SOURCES
Name of source Street address City Postal code Country
Inserm ANRS 101 rue de Tolbiac Paris 75013 France
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Inserm ANRS 101 rue de Tolbiac Paris 75013 France National Public Research Agency
COLLABORATORS
Name Street address City Postal code Country
University of Bordeaux 351 cours de la Liberation Talence Cedex 33405 France
Programme PACCI CHU de Treichville 18 BP 1954 Abidjan 00018 Cote Divoire
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Serge Eholie sergeholie@yahoo.fr 0022521755960 Programme PACCI 18 BP 1954
City Postal code Country Position/Affiliation
Abidjan 00018 Cote Divoire Professor of Infectious and Tropical Diseases at Treichville University Teaching Hospital
Role Name Email Phone Street address
Principal Investigator Fabrice Bonnet fabrice.bonnet@chu-bordeaux.fr 0033556795826 BPH 146 rue Leo Saignat
City Postal code Country Position/Affiliation
Bordeaux Cedex 33076 France Professor of Internal Medicine University of Bordeaux
Role Name Email Phone Street address
Public Enquiries Vanessa Machault vanessa.machault@u-bordeaux.fr 335400008376 351 cours de la Liberation
City Postal code Country Position/Affiliation
Talence Cedex 33405 France Project manager
Role Name Email Phone Street address
Scientific Enquiries Frederic Ello ellonogboufrdric@yahoo.fr 0022521755960 Programme PACCI 18 BP 1954
City Postal code Country Position/Affiliation
Abidjan Cote Divoire Project manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Collection of the following participants’ data: 1. Pre-inclusion/inclusion: date, birth date or age, sex, country of origin, date of first symptoms, symptoms and severity of symptoms, ongoing treatments, chronical diseases, trial treatment. 2. Follow-up: clinical examination results, symptoms, biological exam results, PCR results, ECG results, chest radiography results, adherence to treatment, adverse events. 3. End of follow-up: date and cause. Study Protocol The IPD will be made available within 6 months after the end of the trial and for a period of 3 years after the end of the trial. Any project for the use of data and/or biological samples from the trial not included in the protocol must be submitted in writing to the Steering Committee (as long as it is not dissolved) and then to the Inserm-ANRS (sponsor), which must give its agreement. These projects must receive the favorable opinion of the ethics committees of the countries concerned. After the dissolution of the scientific council, the use of the data and of the biobank will be subject to the rules defined by the Inserm-ANRS. The samples or data may be transferred free of charge to other national or international private or public research teams, under guarantees ensuring their confidentiality and provided for in a transfer agreement between the sponsor and the recipient(s). The data may also be transferred to French or foreign health authorities.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 09/07/2020 Adding temporal precision about the inclusion criteria (i. e. clinical manifestations that started less than 7 days ago). - 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. - 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. - 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.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Plan to share IPD 10/07/2020 The initial trail registration information did not include statement on IPD sharing. The section has been reviewed according to the trial review comment to meet this requirement. Undecided Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 10/07/2020 The initial trail registration information did not include statement on IPD sharing. The section has been reviewed according to the trial review comment to meet this requirement. Collection of the following participants’ data: 1. Pre-inclusion/inclusion: date, birth date or age, sex, country of origin, date of first symptoms, symptoms and severity of symptoms, ongoing treatments, chronical diseases, trial treatment. 2. Follow-up: clinical examination results, symptoms, biological exam results, PCR results, ECG results, chest radiography results, adherence to treatment, adverse events. 3. End of follow-up: date and cause.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 10/07/2020 The initial trail registration information did not include statement on IPD sharing. The section has been reviewed according to the trial review comment to meet this requirement. The IPD will be made available within 6 months after the end of the trial and for a period of 3 years after the end of the trial.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 10/07/2020 The initial trail registration information did not include statement on IPD sharing. The section has been reviewed according to the trial review comment to meet this requirement. Any project for the use of data and/or biological samples from the trial not included in the protocol must be submitted in writing to the Steering Committee (as long as it is not dissolved) and then to the Inserm-ANRS (sponsor), which must give its agreement. These projects must receive the favorable opinion of the ethics committees of the countries concerned. After the dissolution of the scientific council, the use of the data and of the biobank will be subject to the rules defined by the Inserm-ANRS. The samples or data may be transferred free of charge to other national or international private or public research teams, under guarantees ensuring their confidentiality and provided for in a transfer agreement between the sponsor and the recipient(s). The data may also be transferred to French or foreign health authorities.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 10/07/2020 The initial trail registration information did not include statement on IPD sharing. The section has been reviewed according to the trial review comment to meet this requirement. Study Protocol