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: pactr.samrc.ac.za
Trial no.: PACTR202010519682638 Date of Approval: 26/10/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Efficay of two hydroxychloroquine based drug combination regimens in comparison to standard of care in The Treatment of Hospitalized COVID-19 Patients
Official scientific title Hydroxychloroquine/Azithromycin/Zinc Combination and Hydroxychloroquine/Lopinavir/Ritonavir/Azithromycin/Zinc combination versus the standard of care in The Treatment of Hospitalized COVID-19 Patients
Brief summary describing the background and objectives of the trial All the treatment regimens available till date are based on either anecdotal evidence or inadequate data, with the attendant risk of complications from drug reactions or drug-drug interactions in addition to unanswered efficacy issues. This study aims to determine the effectiveness of Hydroxychloroquine and Lopinavir/Ritonavir-based combination regimens in hospitalized COVID-19 patients.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) HCBASE
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 27/08/2020
Actual trial start date
Anticipated date of last follow up 01/03/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 210
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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 Simple randomization using a randomization table from a statistics book Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Hydroxychloroquine combination arm Hydroxychloroquine 400mg twice daily Azithromycin = 500mg daily Zinc Sulphate = 220mg daily Hydroxychloroquine for 10 days Azithromycin for 3 days Zinc Sulphate for 10 days Chloroquine phosphate: Oral chloroquine tablets contain 200 mg of chloroquine salt. To administer 500 mg of chloroquine, two and a half tablets will be given. The tablets are round and appear white. Tablets will need to be reconstituted as liquid preparations for patients who have difficulty in swallowing. For unconscious patients, chloroquine can be crushed and administered as a suspension via a nasogastric tube. Azithromycin: Capsules or tablets containing 250 or 500 mg azithromycin. Dry powder preparations for reconstitution as a suspension for children are also available and this may be used in patients who cannot swallow the capsules. Zinc sulfate: Commonly present as 20 mg oral tablets. To administer 50 mg of zinc, two and a half tablets will be given. The tablets are round and appear white. Tablets will need to be reconstituted as liquid preparations for patients who have difficulty in swallowing 70
Experimental Group Lopinivir retonivir based Azithromycin = 500mg daily Zinc Sulphate = 220mg daily LPV/r = 400/100mg twice daily AZT = 3 days LPV/r = 3 weeks Zn= 10 days Azithromycin is an azalide, derived from erythromycin, and a member of a subclass of macrolide antibiotics with bactericidal and bacteriostatic activities.. .Zinc is an essential micronutrient, with strictly regulated systemic and intracellular concentrations, and it is physiologically needed for an effective antiviral response. It is the second-most abundant trace metal in the human body after iron and an essential component of protein structure and function. Zinc is a general stimulant of antiviral immunity [3027]. Although zinc possesses direct antiviral properties (e.g. influenza), it is also critical in generating both innate and acquired (humoral) antiviral responses. Zinc treatment applied at a therapeutic dose and in the right form has the potential to drastically improve the clearance of both chronic and acute viral infections, as well as their accompanying pathologies and symptoms ..Lopinavir/ritonavir, is a fixed dose combination medication for the treatment and prevention of HIV/AIDS. It combines lopinavir with a low dose of ritonavir. It is a protease inhibitor. Lopinavir/ritonavir, sold under the brand name Kaletra among others, is a fixed dose combination medication for the treatment and prevention of HIV/AIDS. It combines lopinavir with a low dose of ritonavir. It 70
Control Group Standard care Zinc Sulphate = 220mg daily Augmentin = 625 mg twice daily Vitamin C = 200mg three times a day Zinc Sulphate = 10 days Augmentin = 5 days Vitamin C = 3 weeks Augmentin is a prescription medicine used to treat the symptoms of many different infections caused by bacteria such as lower respiratory tract infections, chronic obstructive pulmonary disease, bacterial sinusitis, animal/human bite wounds, and skin infections. Vitamin C, also known as ascorbic acid and ascorbate, is a vitamin found in various foods and sold as a dietary supplement. It is used to prevent and treat scurvy. Vitamin C is an essential nutrient involved in the repair of tissue and the enzymatic production of certain neurotransmitters. Vitamin C is a strong antioxidant that can boost your blood antioxidant levels. This may help reduce the risk of chronic diseases 70 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
. Hospitalized patients with PCR- documented SARS-CoV-2 RNA from throat /nasopharyngeal swab, samples 2. Aged between 18-80 years old 3. the weight is more than 30kg, and there is no limit for men and women 4. Patients who meet the following conditions: creatinine ≤ 110 umol / L, creatinine clearance rate (EGFR) ≥ 60 ml / min / 1.73m2, 5. AST and ALT ≤ 5 × ULN 6. TBIL ≤ 2 × ULN; 7. Patients who are able to fully understand the purpose, nature, method of the study and the possible reactions to the study drugs, voluntarily participate in the study and sign the informed consent 8. Not having severe acute respiratory syndrome (SARS) 9. Patients not using mechanical ventilation or supplemental oxygen, with peripheral oxygen saturation >94% in room air, and having a respiratory rate below 24 incursions per minute. 6. A Normal ECG Baseline result which remains same throughout the study. 1.Hypersensitivity reaction to chloroquine, 4-aminoquinolines or azithromycin and ivermectin 2.Shortness of breath in resting position 3. Known prolonged QT syndrome 4. Active or clinically significant cardiac disease including congestive heart failure. 5. History or current evidence of clinically significant cardiac arrhythmia, atrial fibrillation or paroxysmal supraventricular tachycardia 6. Use of concomitant medications that prolong the QT/QTc interval 7. Elevated levels of troponin I, Creatinine kinase MB, and Myoglobin 8. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency 9. Already receiving chloroquine or azithromycin 10. Patients with other viral pneumonia 11. Patients who have received organ transplantation or surgery planning in the past 6 months 12. Patients who can't take food or drugs due to coma or intestinal obstruction 13. Patients who have severe underlying diseases that affect survival including uncontrolled malignant tumor with multiple metastases that cannot be resected, blood diseases, dyscrasia, active bleeding and severe malnutrition 14. Patients that are pregnant or lactating 15. Patients (including male Patients) having a pregnancy plan (including plans for sperm donation or egg donation) 16. Patients that may fail to take effective contraceptive measures within the next 6 months 17. Patients with allergies to macrolides and chloroquine tablets 18. Patients with contraindications to the test drugs. 19. Patients who are using drugs that interact with the test drugs. 20. Patients using drugs associated with severe and/or life-threatening events [with a narrow therapeutic index] 21. Patients with cirrhosis or pancreatitis 22. Patients with Creatinine QUOTE >110 umol/l 23. Patients with decreased liver function 24. Patients who in the opinion of the investigators after assessing all relevant parameters are unsuitable for the study. Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 80 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 10/08/2020 University of Abuja Teaching Hospital Health Research Ethics Committee UATH HREC
Ethics Committee Address
Street address City Postal code Country
University of Abuja, Gwagwalada, FCT Nigeria Gwagwalada, Abuja 902101 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The rate of virus inhibition [Time Frame: Day 0, 4, 7, 14 and 21] Novel coronaviral nucleic acid is measured in nose / throat swab at each time point. Time (days) from randomization to recovery defined as Absence of symptoms of greater than mild severity for 24 hours Not requiring supplemental oxygen beyond pre-COVID baseline 21 days
Secondary Outcome 1. The disease prorogation-temperature [Time Frame: Day 0 till day 21] 2. Body temperature will be followed every day during time frame. Absence of fever, defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications 3. The disease prorogation-respiratory function 1 [Time Frame: Day 0 till day 21] 4. Respiratory rate will be followed every day during time frame. 5. The disease prorogation-respiratory function 2 [Time Frame: Day 0 till day 21] 6. Oxygen saturation of blood will be followed every day during time frame. 21 days
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of Abuja Teaching Hospital Gwagwalada, Federal Capital Territory Abuja Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institute for Pharmaceutical Research and Development NIPRD Street, Idu Abuja 90001 Nigeria
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor National Institute for Pharmaceutical Research and Development NIPRD NIPRD street, Idu Industrial Estate Abuja 90001 Nigeria Publicly owned research Institute and a publicly owned hospital
COLLABORATORS
Name Street address City Postal code Country
University of Abuja teaching Hospital Hospital street Gwagwalada Gwagwalada Abuja Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Vivian Kwaghe viaarah@yahoo.com +2347057907110 Hospital street
City Postal code Country Position/Affiliation
Gwagwalada Abuja Nigeria Consultant University of Abuja Teaching Hospital
Role Name Email Phone Street address
Scientific Enquiries Margaret Ekpenyong megprid@yahoo.com +2348023206371 NIPRD Street Idu Industrial Estate
City Postal code Country Position/Affiliation
Abuja Nigeria Director NIPRD
Role Name Email Phone Street address
Public Enquiries Olobayo Kunle kunleoo@hotmail.com +2348033145095 NIPRD Street Idu Industrial estate
City Postal code Country Position/Affiliation
Abuja 90001 Nigeria Research Professor National Institute for Pharmaceutical Research and Development
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participants data that underlie the results reported in this article after de-identification Analytic Code,Statistical Analysis Plan,Study Protocol Beginning 9 months and ending 36 months following article publication Investigators whose proposed use of data has been approved by an independent review committee identified for that purpose
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Http//:info@niprd.gov.ng 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