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.: PACTR202008855701534 Date of Approval: 13/08/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title The Nitazoxanide Plus Atazanavir for COVID-19 Study
Official scientific title A Randomized, Open Label Trial to Investigate the Efficacy and Safety of Nitazoxanide Plus Atazanavir/Ritonavir for the Treatment of COVID-19: a Pilot Study
Brief summary describing the background and objectives of the trial Since the outbreak of the novel coronavirus disease in 2019 (COVID-19), an unprecedented global search for potential therapeutics and vaccines is ongoing. In this study, a combination of two drugs that have been shown to be effective against the germ that causes COVID-19 in the laboratory will be tested in patients diagnosed with moderate to severe COVID-19. One of the drugs is called nitazoxanide and the second is atazanavir/ritonavir. Nitazoxanide has been used for the treatment of diarrhea since 2004 while atazanavir/ritonavir was approved for HIV treatment in 2003. They are known to be safe in humans. In this pilot study, 98 COVID-19 patients will be recruited into two group. The 49 patients in group 1 will receive the standard of care determined by their primary care providers while the 49 patients will receive both the standard of care combined with the two study drugs. Patients in group 2 will receive the study drugs for 14 days and all patients will be monitored for a total of 28 days. The time it takes for the germ that causes COVID-19 to be completely removed from the body (in nasal secretions) and the time to clinical improvement will be monitored in all patients and compared between the two groups.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) NACOVID
Disease(s) or condition(s) being studied Infections and Infestations,Respiratory
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Treatment: Drugs
Anticipated trial start date 21/09/2020
Actual trial start date
Anticipated date of last follow up 21/01/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 98
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL https://clinicaltrials.gov/ct2/show/NCT04459286
Secondary Ids Issuing authority/Trial register
NCT04459286 clinicaltrials.gov
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 Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Nitazoxanide and atazanavirritonavir Nitazoxanide: 1000 mg twice daily Atazanavir/ritonavir: 300/100 mg once daily 14 days Patients in the intervention group will receive 1000 mg nitazoxanide tablets twice daily and 300/100 mg atazanavir/ritonavir tablets once daily with meal, in addition to standard of care which will be determined by their primary care provider 49
Control Group Standard of care 14 days Standard of care will be as determined by the clinical team at the treatment centres in line with the current National Interim Guidelines for Clinical Management of COVID-19 49 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Willingness and ability to provide written informed consent At least 18 and not more than 75 years of age at study entry SARS-CoV-2 infection confirmed by PCR test within 4 days before randomization Currently symptomatic (fever or chills, cough, myalgia, sore throat, shortness of breath, or new onset of anosmia or ageusia) and at COVID-19 isolation and treatment centre Inability to take orally administered medication or food Known hypersensitivity to study medication Pregnant or lactating (unless practicing exclusive replacement feeding for the entire study duration) Participation in any other interventional trial for COVID-19 (observational study co-enrollment allowed) Concurrent treatment with other agents with actual or possible direct-acting antiviral activity against SARS-CoV-2 less than 24 hours prior to study drug dosing Concurrent use of agents with known or uncertain interaction with study drugs, including ritonavir Requiring mechanical ventilation at screening Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) above 5 times upper limit of normal (ULN) Creatinine clearance below 50 mL/min using the Cockcroft-Gault formula for participants above 18 years of age Recent history of or currently having a noncommunicable disease (e.g. cardiovascular disease, cancer, chronic respiratory diseases and diabetes) Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 75 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
Yes 26/08/2020 National Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Federal Ministry of Health, Federal Secretariat Complex Abuja 220005 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Time to clinical improvement - Proportion of patients with clinical improvement, as defined by live discharge from the hospital, a decrease of at least 2 points from baseline on a 7-point ordinal scale, or both. Day 3, Day 7, Day 10, Day 14, Day 21, Day 28
Primary Outcome Time to SARS-CoV-2 negativity - Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result Day 2, Day 4, Day 6, Day 7, Day 14, Day 28
Primary Outcome Difference in SARS-CoV-2 AUC - Temporal patterns of SARS-CoV-2 viral load quantified by RT-PCR from nasal swabs or sputum of patients receiving SOC alone versus SOC plus study drug Day 2, Day 4, Day 6, Day 7, Day 14, Day 28
Secondary Outcome Time to symptoms resolution - Time to symptoms resolution as monitored by the Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) questionnaire with some modifications for COVID-19 Days 1-14, 21, 28
Secondary Outcome Clinical status as assessed with the seven-category ordinal scale Day 7, Day 14
Secondary Outcome Duration of hospitalization in survivors Day 28
Secondary Outcome Day 28 mortality Day 28
Secondary Outcome Time from treatment initiation to death Day 28
Secondary Outcome Proportion with viral RNA detection over time Day 28
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Infectious Disease Hospital Olodo Ibadan Nigeria
COVID19 Isolation and Treatment Centre Obafemi Awolowo University Teaching Hospitals Complex Ile Ife Nigeria
State Specialist Hospital Asubiaro Osogbo Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
University of Liverpool Brownlow Hill Liverpool United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Obafemi Awolowo University Obafemi Awolowo University Ile Ife Nigeria University
COLLABORATORS
Name Street address City Postal code Country
Professor Christian Happi African Center of Excellence for Genomics of Infectious Diseases Ede Nigeria
Professor Andrew Owen University of Liverpool Liverpool United Kingdom
Professor Oluseye Bolaji Obafemi Awolowo University Ile Ife Nigeria
Professor Adedeji Onayade Obafemi Awolowo University and Obafemi Awolowo University Teaching Hospital Ile Ife Nigeria
Dr Adeola Fowotade Infectious Diseases Hospital, Olodo and University of Ibadan Ibadan Nigeria
Dr Akindele Olupelumi Adebiyi University of Ibadan and Infectious Diseases Hospital, Olodo Ibadan Nigeria
Dr Olabode Ladipo Oyo State Ministry of Health Ibadan Nigeria
Dr Ajibola Olagunoye State Specialist Hospital Osogbo Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Adeniyi Olagunju aeolagunju@oauife.edu.ng +2349068858698 Obafemi Awolowo University
City Postal code Country Position/Affiliation
Ile Ife Nigeria Senior Lecturer Obafemi Awolowo University
Role Name Email Phone Street address
Public Enquiries Francis Adesina fadesina@oauife.edu.ng +2348037193141 Obafemi Awolowo University
City Postal code Country Position/Affiliation
Ile Ife Nigeria Director Central Office of Research
Role Name Email Phone Street address
Scientific Enquiries Adeniyi Olagunju aeolagunju@oauife.edu.ng +2349068858698 Obafemi Awolowo University
City Postal code Country Position/Affiliation
Ile Ife Nigeria Senior Lecturer Obafemi Awolowo University
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary results will be provided within the trial registration as they become available. Access to disaggregated and anonymised data may be granted upon request. Informed Consent Form Within 12 months of study completion Summary data will be made open access. However, request for access to disaggregated and anonymised data will be assessed on a case by case basis, depending on the qualifications of the requester, quality of request and type of secondary analysis proposed.
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
Reporting Plan to share IPD 12/08/2020 Now a mandatory requirement prior to registration Undecided Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 12/08/2020 Now a mandatory requirement prior to registration Summary results will be provided within the trial registration as they become available. Access to disaggregated and anonymised data may be granted upon request.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 12/08/2020 Now a mandatory requirement prior to registration Within 12 months of study completion
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 12/08/2020 Now a mandatory requirement prior to registration Summary data will be made open access. However, request for access to disaggregated and anonymised data will be assessed on a case by case basis, depending on the qualifications of the requester, quality of request and type of secondary analysis proposed.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 12/08/2020 Now a mandatory requirement prior to registration Informed Consent Form
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 01/09/2020 Ethics approval granted TRUE, National Health Research Ethics Committee, Federal Ministry of Health, Federal Secretariat Complex, Abuja, 220005, Nigeria, , 26 Aug 2020, +2348063190328, deskofficer@nhrec.net, 12266_11671_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 01/09/2020 Unanticipated delay 01 Sep 2020 21 Sep 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 01/09/2020 Unanticipated delay 28 Feb 2021 21 Jan 2021
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 01/09/2020 Duplicate entry