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.: PACTR202012898601759 Date of Approval: 04/12/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title PHASE 2 TRIAL: EVALUATION OF SILYMARIN FOR TREATMENT OF PATIENTS WITH COVID-19
Official scientific title EVALUATION OF THE INHIBITORY ACTIVITIES OF SILYMARIN AGAINST SARS-CoV-2 . COVID-19
Brief summary describing the background and objectives of the trial Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (previously called 2019 novel coronavirus (2019-nCoV) is the causative agent of coronavirus disease 2019 (COVID-19), a viral disease recently declared a global public health emergency by the World Health Organization. Several treatment options have been developed or repurposed for treatment of COVID 19. Silymarin, an extract from the seed of the milk thistle plant (Silybum marianum [S. marianum]) is widely known for its hepatoprotective functions, mainly due to its anti-oxidative, anti-inflammatory, and immunomodulatory effects. Although silymarin is known mostly for its hepatoprotective functions, accumulating evidence now suggests that the extract possesses potent antiviral activities against numerous viruses, particularly hepatitis C virus (HCV). Despite the clear antiviral effects of silymarin and silymarin-derived compounds on HCV in vivo and in vitro, the mechanism(s) of action remain incompletely understood. Silymarin (a flavonoid) has also been shown to have antiplasmodial effect against Plasmodium falciparum the causative agent of malaria (Basu and Sahi 2017). Consequently it is very probable there exists a crosstalk between silymarin antimalarial mechanisms and its antiviral activity – potentially SARS-CoV-2, additionally we carried out molecular docking studies on silymarin which revealed binding energies with SARS-CoV-2 spike glycoprotein (S) and main protease (Mpro) pathogenicity determinants that are near identical with the binding energies of CQ/HQ ( drugs undergoing clinical trial for the treatment of COVID-19. Aim: To evaluate the effect of silymarin on SARS-CoV-2 in Nigeria. General Objectives: To evaluate the inhibitory effects of silymarin on SARS CoV-2 Specific Objectives: 1. To determine the antiviral effect of Silymarin in cell lines 2. To assess the toxicity profile of silymarin in Drosophila melanogaster model 3. To evaluate the efficacy and safety
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ESTC
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 20/12/2020
Actual trial start date
Anticipated date of last follow up 27/08/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 314
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL https://www.biorxiv.org/content/10.1101/2020.03.31.017657v2
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 created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Silymarin based combination 140mg orally at 8 hourly 7 days Intervention group: Silymarin-based combination: Silymarin + Chloroquine/Hydroxychloroquine, Azithromycin + Vitamin-C + Vitamin- E + Zinc sulphate and Dexamethasone. 157
Control Group Chloroquine 1g stat then 500mg daily 5 days Standard of care: Chloroquine + Azithromycin + Vitamin-C + Vitamin-E + Zinc-sulphate and dexamethasone 157 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Positive SARS COV-2 RT-PCR 2. Age > 6 weeks and above 2. Had not received any of the study drugs for at least one day 1. Unable to take oral medications 2. Pregnancy 4. Severe immunocompromised 5. Known contraindications to study drugs 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 6 Week(s) 99 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 01/12/2020 National Health Research Ethics Committee of Nigeria NHREC
Ethics Committee Address
Street address City Postal code Country
Federal Ministry of Health, New Federal Secretariat Complex, Ahmadu Bello Way, Phase III, Abuja Abuja 900247 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Clinical recovery from start of treatment 14 days
Secondary Outcome Viral clearance (SARS COV 2 RT-PCR) at days 0, 7 and 14
Secondary Outcome Safety and tolerability: days 0, 7 and 14
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Jos University Teaching Hospital Lamingo Jos 930242 Nigeria
Plateau State Specialist Hospital 2a Gomwalk Rd Jos 930262 Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
Tertiary Education Trust Fund TETFUND Special Intervention COVID19 Grant NO 6 Zambezi Crescent, Off Aguiyi Ironsi Street, Maitama Abuja 900271 Nigeria
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Africa Centre of Excellence in Phytomedicine Research and Development ACEPRD Africa Centre of Excellence in Phytomedicine Research and Development, No. 1, Road 4, University of Jos Senior Staff Quarters, Jos 930001 Nigeria University
Secondary Sponsor Jos University Teaching Hospital Lamingo Jos 930242 Nigeria Hospital
COLLABORATORS
Name Street address City Postal code Country
National Veterinary Research Institute Off Vom road Jos 930103 Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Nathan Shehu nyshehu@yahoo.com +2347030555239 Medicine Department Jos University Teaching Hospital
City Postal code Country Position/Affiliation
Jos 930242 Nigeria Clinical study lead ID Physician
Role Name Email Phone Street address
Principal Investigator John Aguiyi jca757@yahoo.com +2348037016418 No. 1, Road 4, University of Jos Senior Staff Quarters, Bauchi Road/Bauchi Ring-Road
City Postal code Country Position/Affiliation
Jos 930001 Nigeria Overall Project lead
Role Name Email Phone Street address
Public Enquiries Simeon Omale soluv04@gmail.com +2348037009165 Africa Centre of Excellence in Phytomedicine Research and Development, No. 1, Road 4, University of Jos Senior Staff Quarters, Bauchi Road/Bauchi Ring-Road
City Postal code Country Position/Affiliation
Jos 930001 Nigeria Safety lead
Role Name Email Phone Street address
Scientific Enquiries Shwe David shwedavid@yahoo.com +2348163480425 Paediatrics Department Jos University Teaching Hospital
City Postal code Country Position/Affiliation
Jos 930242 Nigeria Consultant Paediatric Infectious Diseases
Role Name Email Phone Street address
Scientific Enquiries Pam Luka pamluka08@gmail.com +2348073919739 National Veterinary Research Institute
City Postal code Country Position/Affiliation
Vom 930103 Nigeria Virologist
Role Name Email Phone Street address
Public Enquiries Emmanuel Nnadi eennadi@gmail.com +2348068124819 Plateau State University Bokkos
City Postal code Country Position/Affiliation
Bokkos 932112 Nigeria Microbiologist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes De-identified individual participant data would be available including data dictionaries; every deidentified individual participant data collected during the trial would be shared; additionally, the study protocol will also be made available); Generated data would be analyzed at every phase of the research and published in open access journal and made available as preprints at each phase and with no end date. Statistical Analysis Plan 3 months of completion access would be granted to classified authorities for scientific and policy making purposes
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
Trial Information Public title 04/12/2020 edit PHASE 2 TRIAL: EVALUATION OF SILYMARIN FOR TREATMENT OF PATIENTS WITH COVID 19 PHASE 2 TRIAL: EVALUATION OF SILYMARIN FOR TREATMENT OF PATIENTS WITH COVID-19
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 04/12/2020 COVID-19 tag added as per WHO-ICTRP request EVALUATION OF THE INHIBITORY ACTIVITIES OF SILYMARIN AGAINST SARS-CoV-2 EVALUATION OF THE INHIBITORY ACTIVITIES OF SILYMARIN AGAINST SARS-CoV-2 . COVID-19