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.: PACTR202006899597082 Date of Approval: 10/06/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Efficacy of a new COVID-19 treatment
Official scientific title Randomized clinical trial, phase 2, to evaluate the efficacy of Artesunate IV alone or combined with vitamin C IV for the treatment of COVID-19
Brief summary describing the background and objectives of the trial Background: The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona 2 (SARS-CoV-2) is a global health emergency with an increasing number of confirmed cases in Madagascar. There are no data available on the efficacy of antivirals for the treatment of COVID-19. Thus, this study aims to assess the safety and efficacy of injectable artesunate alone and artesunate IV+ Vitamin C IV in reducing viral load in patients with COVID-19. This is a randomized clinical trial in patients identified as COVID-19 positive by PCR analysis with moderate symptoms. The study population is made up of adult subjects, aged 18 to 70 years. COVID-19 infection will be identified through extensive population screening initiated by the Ministry of Health. The study will be carried out in the Voara village located in Andohatapenaka which is a site developed by the Malagasy State specifically to host this clinical trial. Treatment will start when the patient registers and will stop after 7 days, or in the event of serious deterioration in health requiring other medical interventions. Expected results: This study will provide a better understanding of the efficacy of injectable artesunate alone and that of injectable artesunate combined with injectable Vitamin C in the form of Na-ascorbate compared with a control arm receiving saline serum isotonic (SSI) to develop new strategies for the management of covid-19
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
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 29/04/2020
Actual trial start date
Anticipated date of last follow up 29/09/2020
Actual Last follow-up date 25/11/2020
Anticipated target sample size (number of participants) 60
Actual target sample size (number of participants) 44
Recruitment status Completed
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Numbered containers Masking/blinding used Care giver/Provider
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Isotonic Saline Serum Seven days 20 people infected with COVID-19 proven by RT-PCR will be receiving isotonic saline serum (ISS) in their treatment 20 Placebo
Experimental Group Artesunate IV Seven days 20 people infected with COVID-19 proven by RT-PCR will be receiving Artesunate IV in their treatment 20
Experimental Group Artesunate IV plus Vit C IV Seven days 20 people infected with COVID-19 proven by RT-PCR and receiving Artesunate IV + Vitamin C IV (Na-ascorbate) in their treatment 20
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Adults aged between 18 to 70 • COVID-19 confirmed by a RT-PCR test in real time 4 days before being enrolled in the clinical trial • Patients with moderate signs of COVID-19 • Patients consenting voluntarily and freely Contraindications to the drug tested • Patients who require breathing apparatus (eg invasive ventilation, invasive mechanical ventilation, oxygenation of the extra-corporeal membrane) • Patients who participated in other clinical trials related to COVID-19 • Patients who received medication directly treating COVID-19 24 hours before the start of the study. Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 70 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 24/04/2020 Biomedical research within the Ministry of Public Health of Madagascar
Ethics Committee Address
Street address City Postal code Country
Tsaralalana Antananarivo 8145 Madagascar
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome This project will provide a better understanding of the efficacy of Artesunate IV alone or combined with Vitamin C in the form of Na-ascorbate compared to ISS in Madagascar in order to develop new strategies for the management of covid -19 adapted to the local context. Clinical efficacy: 15th day Viral load: 21th day
Secondary Outcome Evaluate viral load during the trial period • Determine the clinical status of patients infected with COVID-19 2 days qRT-PCR / Viral load / Clinical symptoms - 3th,5th,8th,10th, 14th, 21th, 28th days of the treatment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Clinical Research Center Andohotapenaka Antananarivo Madagascar
FUNDING SOURCES
Name of source Street address City Postal code Country
Malagasy government Ambotsirohitra Antananarivo Madagascar
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Malagasy government Ambotsirohitra Antananarivo Madagascar Government
COLLABORATORS
Name Street address City Postal code Country
Dhanjay Jhurry University of Mauritius Reduit 80837 Mauritius Mauritius
Nathan Goodyear An Oasis of Healing Clinic 210 N, Center St 102, Mesa, Arizona 85201 Arizona United States of America
Thomas Lodi The Lifeco, 75 Moo 3 Sakoo, Thalang, Phuket 83110 Phuket Thailand
Archana Bhaw Luximon Centre for Biomedical and Biomaterials Research, University of Mauritius, 80837 Reduit Mauritius Mauritius
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator RAKOTOVAO Andriamiadana Luc lucdina007@yahoo.fr +261341420157 By-pass Iavoloha
City Postal code Country Position/Affiliation
Antananarivo Madagascar Professor MD University of Antananarivo
Role Name Email Phone Street address
Principal Investigator RAMANITRAHASIMBOLA David dramanitrahasimbola@yahoo.fr +261346369034 Ilafy
City Postal code Country Position/Affiliation
Antananarivo Madagascar Professor PharmaD University of Antananarivo
Role Name Email Phone Street address
Scientific Enquiries RATSIMBASOA Claude Arsene aratsimbasoa@gmail.com +261340541965 Andrononobe Analamahitsy
City Postal code Country Position/Affiliation
Antananarivo Madagascar Professor MD PhD University of Fianarantsoa
Role Name Email Phone Street address
Public Enquiries MIORAMALALA Sedera sedera.mioramalala@gmail.com +261341057733 Itaosy
City Postal code Country Position/Affiliation
Antananarivo Madagascar MD
Role Name Email Phone Street address
Scientific Enquiries RAKOTOARIVELO Rivonirina Andry rakotoarivelo.rivo@yahoo.fr +261345318757 CHU Tambohobe
City Postal code Country Position/Affiliation
Fianarantsoa Madagascar Professor MD specialist in infectious diseases University of Fianarantsoa
Role Name Email Phone Street address
Scientific Enquiries RAPELANORO RABENJA Fahafahantsoa frapelanoro@gmail.com +261320519476 University of Antananarivo
City Postal code Country Position/Affiliation
Antananarivo Madagascar Professor MD University of Antananarivo
Role Name Email Phone Street address
Scientific Enquiries RAKOTO Rafanomezantsoa rakotofanomezantsoa@yahoo.fr +261340787097 Military Hospital of Soavinandriana
City Postal code Country Position/Affiliation
Antananarivo Madagascar Professor MD General of the Army
Role Name Email Phone Street address
Scientific Enquiries RAKOTOSAONA Riana rravalison@gmail.com +261341169436 Centre National d Application de Recherches Pharmaceutiques
City Postal code Country Position/Affiliation
Antananarivo Madagascar PhD CNARP Director
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We collect the following participants data: Birth date, sex, entry date, 1- Treatment before inclusion, 2- On inclusion: symptoms, clinical signs, biological exam results, PCR result, chest radiography results, ECG result, 3- During follow up: symptoms, clinical signs, biological exam results, PCR result, chest radiography result, ECG result, unwanted events. Clinical Study Report,Informed Consent Form,Study Protocol IPD/Additional documents will be available for sharing at the end of the study and during five years. The access is controlled by the sponsor which is the Malagasy government. The types of data analysis permitted are also under the control of the Malagasy government and the steps for requesting the document is to contact the principals investigators or the scientific committee
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 Official scientific title 09/06/2020 edit Randomized clinical trial, phase 2, to evaluate the efficacy of injectable artesunate alone or combined with vitamin C for the treatment of covid-19 Randomized clinical trial, phase 2, to evaluate the efficacy of injectable artesunate alone or combined with vitamin C for the treatment of COVID-19
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 09/06/2020 We mistranslated Randomized clinical trial, phase 2, to evaluate the efficacy of injectable artesunate alone or combined with vitamin C for the treatment of COVID-19 Randomized clinical trial, phase 2, to evaluate the efficacy of Artesunate IV alone or combined with vitamin C IV for the treatment of COVID-19
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 09/06/2020 We mistranslated Background: The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona 2 (SARS-CoV-2) is a global health emergency with an increasing number of confirmed cases in Madagascar. There are no data available on the efficacy of antivirals for the treatment of COVID-19. Thus, this study aims to assess the safety and efficacy of injectable artesunate alone and injectable artesunate + injectable Vitamin C in reducing viral load in patients with COVID-19. This is a randomized clinical trial in patients identified as COVID-19 positive by PCR analysis with moderate symptoms. The study population is made up of adult subjects, aged 18 to 70 years. COVID-19 infection will be identified through extensive population screening initiated by the Ministry of Health. The study will be carried out in the Voara village located in Andohatapenaka which is a site developed by the Malagasy State specifically to host this clinical trial. Treatment will start when the patient registers and will stop after 7 days, or in the event of serious deterioration in health requiring other medical interventions. Expected results: This study will provide a better understanding of the efficacy of injectable artesunate alone and that of injectable artesunate combined with injectable Vitamin C in the form of Na-ascorbate compared with a control arm receiving saline serum isotonic (SSI) to develop new strategies for the management of covid-19 Background: The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona 2 (SARS-CoV-2) is a global health emergency with an increasing number of confirmed cases in Madagascar. There are no data available on the efficacy of antivirals for the treatment of COVID-19. Thus, this study aims to assess the safety and efficacy of injectable artesunate alone and artesunate IV+ Vitamin C IV in reducing viral load in patients with COVID-19. This is a randomized clinical trial in patients identified as COVID-19 positive by PCR analysis with moderate symptoms. The study population is made up of adult subjects, aged 18 to 70 years. COVID-19 infection will be identified through extensive population screening initiated by the Ministry of Health. The study will be carried out in the Voara village located in Andohatapenaka which is a site developed by the Malagasy State specifically to host this clinical trial. Treatment will start when the patient registers and will stop after 7 days, or in the event of serious deterioration in health requiring other medical interventions. Expected results: This study will provide a better understanding of the efficacy of injectable artesunate alone and that of injectable artesunate combined with injectable Vitamin C in the form of Na-ascorbate compared with a control arm receiving saline serum isotonic (SSI) to develop new strategies for the management of covid-19
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 19/03/2021 Data clearance 25 Nov 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 19/03/2021 difficult recruitment 44
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 19/03/2021 study completed Not yet recruiting Completed
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 10/06/2020 Updates Clinical Research Center, Voara Village Andohotapenaka - Near Hospital Manarapenitra, Antananarivo, , Madagascar Clinical Research Center , Andohotapenaka, Antananarivo , , Madagascar
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 10/06/2020 Missiing information Thomas Lodi, Oasis International, Bangkok, , Thailand Thomas Lodi, The Lifeco, 75 Moo 3 Sakoo, Thalang, Phuket 83110, Bangkok, , Thailand
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 09/06/2020 We forgot to add Dhanjay Jhurry, University of Mauritius Reduit 80837, Mauritius, , Mauritius
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 09/06/2020 We forgot to add Nathan Goodyear, An Oasis of Healing Clinic, Arizona, , United States of America
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 10/06/2020 Missing information Nathan Goodyear, An Oasis of Healing Clinic, Arizona, , United States of America Nathan Goodyear, An Oasis of Healing Clinic 210 N, Center St 102, Mesa, Arizona 85201, Arizona, , United States of America
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 09/06/2020 We forgot to add Thomas Lodi, Akesis Life, Bangkok, , Thailand
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 09/06/2020 We got the wrong information Thomas Lodi, Akesis Life, Bangkok, , Thailand Thomas Lodi, Oasis International, Bangkok, , Thailand
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 10/06/2020 Missing information Thomas Lodi, Oasis International, Bangkok, , Thailand Thomas Lodi, The Lifeco, 75 Moo 3 Sakoo, Thalang, Phuket 83110, Bangkok, , Thailand
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 10/06/2020 Wrong information Thomas Lodi, The Lifeco, 75 Moo 3 Sakoo, Thalang, Phuket 83110, Bangkok, , Thailand Thomas Lodi, The Lifeco, 75 Moo 3 Sakoo, Thalang, Phuket 83110, Phuket, , Thailand
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 10/06/2020 We forgot to add Archana Bhaw Luximon, Centre for Biomedical and Biomaterials Research, University of Mauritius, 80837 Reduit, Mauritius, , Mauritius
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 10/06/2020 There was some error Scientific Enquiries, RATSIMBASOA, Claude Arsene, Prof., aratsimbaosa@gmail.com, , +261340541965, Andrononobe Analamahitsy, Antananarivo, , Madagascar, Professor MD PhD University of Fianarantsoa Scientific Enquiries, RATSIMBASOA, Claude Arsene, Prof., aratsimbasoa@gmail.com, , +261340541965, Andrononobe Analamahitsy, Antananarivo, , Madagascar, Professor MD PhD University of Fianarantsoa
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 11/06/2020 Updates Scientific Enquiries, RAKOTOARIVELO, Rivonirina Andry, Prof., rakotoarivelo.rivo@yahoo.fr, , +261345318757, CHU Tambohobe , Fianarantsoa, , Madagascar, Professor MD specialist in infectious diseases University of Fianarantsoa
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 11/06/2020 Updates Scientific Enquiries, RAPELANORO RABENJA, Fahafahantsoa, Prof., frapelanoro@gmail.com, , +261320519476, University of Antananarivo, Antananarivo, , Madagascar, Professor MD University of Antananarivo
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 11/06/2020 Updates Scientific Enquiries, RAKOTO, Rafanomezantsoa, Prof., rakotofanomezantsoa@yahoo.fr, , +261340787097, Military Hospital of Soavinandriana, Antananarivo, , Madagascar, Professor MD General of the Army
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 11/06/2020 Update Scientific Enquiries, RAKOTOSAONA, Riana, Dr., rravalison@gmail.com, , +261341169436, Centre National d Application de Recherches Pharmaceutiques, Antananarivo, , Madagascar, CNARP Director
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 11/06/2020 Update Scientific Enquiries, RAKOTOSAONA, Riana, Dr., rravalison@gmail.com, , +261341169436, Centre National d Application de Recherches Pharmaceutiques, Antananarivo, , Madagascar, CNARP Director Scientific Enquiries, RAKOTOSAONA, Riana, Dr., rravalison@gmail.com, , +261341169436, Centre National d Application de Recherches Pharmaceutiques, Antananarivo, , Madagascar, PhD CNARP Director
Section Name Field Name Date Reason Old Value Updated Value
Reporting Plan to share IPD 09/06/2020 We now plan to share the IPD No Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 09/06/2020 We now plan to share the IPD We collect the following participants data: Birth date, sex, entry date, 1- Treatment before inclusion, 2- On inclusion: symptoms, clinical signs, biological exam results, PCR result, chest radiography results, ECG result, 3- During follow up: symptoms, clinical signs, biological exam results, PCR result, chest radiography result, ECG result, unwanted events.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 09/06/2020 We now plan to share the IPD IPD/Additional documents will be available for sharing at the end of the study and during five years.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 09/06/2020 We now plan to share the IPD The access is controlled by the sponsor which is the Malagasy government. The types of data analysis permitted are also under the control of the Malagasy government and the steps for requesting the document is to contact the principals investigators or the scientific committee
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 09/06/2020 We now plan to additional Document Types Study Protocol, Informed Consent Form, Clinical Study Report