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.: PACTR202011812241529 Date of Approval: 30/11/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title EFFICACY AND SAFETY OF PYRONARIDINE-ARTESUNATE (PYRAMAX) FOR THE TREATMENT OF FALCIPARUM MALARIA IN AFRICAN PREGNANT WOMEN
Official scientific title EFFICACY AND SAFETY OF PYRONARIDINE-ARTESUNATE (PYRAMAX) FOR THE TREATMENT OF FALCIPARUM MALARIA IN AFRICAN PREGNANT WOMEN
Brief summary describing the background and objectives of the trial Methodology This is a Phase 3, non-inferiority (95% efficacy and a non-inferiority margin of 5%), multicentre (Burkina Faso, Democratic Republic of Congo, Mali, Mozambique, The Gambia), randomised, open-label clinical trial. Pregnant women with malaria will be randomised to one of three arms to be treated with pyronaridine-artesunate, artemether-lumefantrine or dihydroartemisinin-piperaquine. Women will be actively followed up until day 63 post-treatment, at delivery, and at 4-6 weeks post-delivery. The infants will be visited around the first birthday to check their health status. Countries Burkina-Faso, Democratic Republic of Congo (DRC), Mali, Mozambique, and The Gambia Study Centers - Burkina-Faso: Nanoro and Boussé - DRC: Lisungi - Mali: Bougoula-Hameau and San - Mozambique: Manhiça Health Research Center - The Gambia: Basse, Demba Kunta Koto, Fatoto, Gambissara and Koina Objectives To determine efficacy, safety, and tolerability of pyronaridine-artesunate (PA) as compared to either artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) when administered to pregnant women with P. falciparum infection during the 2nd or 3rd trimester. Specific objectives are the following: 1) To compare the efficacy of PA against AL or DP in terms of: a. Treatment success (see definition below) at 28, 42 and 63 days after the start of treatment, with and without genotyping; b. Parasite clearance time, including sub-microscopic malaria infections; c. Gametocyte carriage and clearance; d. Haematological recovery by 14, 28, 42 and 63 days post-treatment and at delivery; e. Birth weight measured within 72 hours of delivery; f. Preventing placenta P. falciparum malaria. 2) To describe the safety profile of PA, AL and DP in terms of: a. Tolerability b. Adverse events, including Serious Adverse Events, during the 63-day post-treatment follow up, at delivery, and one month and one year post-end of pregnancy.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) PYRAPREG
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/07/2020
Actual trial start date 01/12/2020
Anticipated date of last follow up 30/06/2023
Actual Last follow-up date 30/12/2023
Anticipated target sample size (number of participants) 2002
Actual target sample size (number of participants) 2002
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
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Pyronaridine Artesunate One daily 3 days The interventional treatment will be Pyronaridine Artesunate. 625
Control Group Artemether Lumefantrine Twice daily 3 days One of the control drug will be Artemether lumefantrine 625 Active-Treatment of Control Group
Control Group Dihydroartemesinin Pyperaquine One daily 3 days The second control treatment will be dihydroartemisinin-piperaquine 625 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Gestation ≥16 weeks and <37 weeks as assessed by ultrasound when possible, uterine height or late menstrual period; 2. P. falciparum mono-infection (by microscopy) of any density, regardless of symptoms and HIV status; 3. Haemoglobin ≥7g/dL; 4. Age: ≥15 years; 5. Residence within the health facility catchment area; 6. Willing to adhere to study requirements and to deliver at the health facility. 7. Ability to provide written informed consent; if the woman is minor of age/not emancipated, the consent must be given by a parent or legal guardian according to national law (however, in this case, the investigator is responsible to check that the woman herself is also freely willing to take part in the study). 8. For the PK study women should be on first line anti-retroviral treatment (efavirenz-based both in DRC and Mozambique) for at least 6 months. 1. Known allergy to the study drugs; 2. History of known pregnancy complications or poor obstetric history such as repeated stillbirths or eclampsia; 3. History or presence of major illnesses likely to influence pregnancy outcome; 4. Any significant illness at the time of screening requiring hospitalization, including a. Severe malaria; b. Any sign or symptom suggesting hepatic lesions (e.g. nausea with abdominal pain and icterus) or severe liver disease classified as B or C by the Child-Pugh score; c. Known history or evidence of clinically significant cardiovascular disorders or family history of long QT syndrome. 5. Intent to move out of the study catchment area before delivery or delivery out of the catchment area; 6. Prior enrolment in the study; 7. Clear evidence of recent (1 week) treatment with antimicrobials with antimalarial activity (azithromycin, clindamycin, tetracycline, quinolones, cotrimoxazole and SP); For HIV-infected pregnant women to be included in the PK sub-study, cotrimoxazole use is not an exclusion criterion. 8. Twin/multiple pregnancy; 9. Known history of G6PD deficiency or sickle cell disease. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year 15 Year(s) 45 Year(s) Female
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 31/03/2020 Faculty of Medicine and Faculty of Pharmacy
Ethics Committee Address
Street address City Postal code Country
Point G Bamako 1805 Mali
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome PCR-adjusted ACPR at Day 42; Day 42
Secondary Outcome - Safety profile, including cardiac and hepatic toxicity, and significant changes in relevant laboratory values. - PCR-adjusted ACPR at Day 28 and 63; - PCR-unadjusted ACPR at Day 28, 42 and 63; - Parasite and fever clearance time; - Gametocyte carriage and clearance; - Haematological recovery, namely Hb changes between Day 0 and Days 7, 14, 28, 42, 63 and at delivery; - Prevalence of placenta malaria at delivery (recent, past and chronic infection); - Mean birth weight BW and prevalence of low birth weight (<2,500g) new-borns. Day 28, Day 42, Day 63, delivery, 4-6 weeks after delivery and 1 year after delivery
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Institut de Recherche en Sciences de la Sante Ouaga CMS 11 Ouagadougou 11 BP218 Burkina Faso
University of Kinshasa Avenue de Universite No1, Commune de Lemba Kinshasa BP : 747 Democratic Republic of the Congo
Malaria Research and Training Center Point G Bamako 1805 Mali
Center for Health Research Manhica Rua 12 Manhica CP 1929 Mozambique
Medical Research Council Unit The Gambia Fajara Banjul Box 273 Gambia
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP 51 2593 HW The Hague Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Sciences Techniques and Technologies of Bamako Hamdalaye ACI 2000 Rue 405 Bamako BP E 423 Mali University
COLLABORATORS
Name Street address City Postal code Country
USTTB Hamdalaye ACI 2000 RUE 405 Bamako BP E 423 Mali
Medical Research Council Unit Fajara Banjul Gambia
ISGlobal Rossello Barcelona Spain
University of Kinshasa Kinshasa Kinshasa Democratic Republic of the Congo
Academisch Medisch Centrum bij de Universiteit van Amsterdam Amsterdam Amsterdam Netherlands
Stichting Het Nederlands Kanker Instituut Antoni van Leeuwenhoek ziekenhuis Amsterdam Amsterdam Netherlands
IRSS Ouagadougou Ouagadougou Burkina Faso
CISM Manhica Manhica Mozambique
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Kassoum Kayentao kayentao@icermali.org +22320228109 Point G
City Postal code Country Position/Affiliation
Bamako Mali PI and Project coordinator
Role Name Email Phone Street address
Public Enquiries Boubacar Traore bouba.traore@icermali.org +22320228109 Point G
City Postal code Country Position/Affiliation
Bamako Mali Dean of the Faculty of Pharmacy
Role Name Email Phone Street address
Scientific Enquiries Abdoulaye Djimde adjimde@icermali.org +22320228109 Point G
City Postal code Country Position/Affiliation
Bamako Mali Director of MRTC
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The five African countries in the PYRAPREG Consortium were selected to represent various malaria transmission patterns in sub-Saharan Africa. Therefore, the results of the PYRAPREG project will be broadly applicable to other African pregnant women at risk of P. falciparum infection. The consortium aims at producing results that will inform WHO policies for the treatment of malaria in pregnancy, so the NMCPs may integrate such changes in their treatment guidelines. This consortium, through its project results, will offer a good opportunity to increase existing data on the efficacy and safety of DP and AL. In addition, the impact of the results of this project is maximised by the fact that the safety data collected will be extremely useful for considering the use of PA for pregnant women infected by other malaria parasites, mainly P. vivax, whose major endemic areas are South America, Southeast Asia and South Pacific. Therefore, for the PYRAPREG consortium, ensuring timely and excellent dissemination pathways is a must, and thus, a dedicated WP has been included in the Project proposal (WP6 Dissemination, Exploitation and Communications, led by UNIKIN with the support of ISGlobal) in order to maximize the impact of this project. Informed Consent Form,Statistical Analysis Plan,Study Protocol The dissemination, exploitation and communication activities have been defined prior to start any activity on site in the Dissemination, Exploitation and Communication Plan (DEC Plan) which will be developed after a careful needs assessment of target audiences, key messages and key dates, platforms, tools and potential alliances. This assessment will be done through an all-investigators’ project forum and will be led and boosted by an expert coach in order to bring out all their expertise. The results of this assessment will be the pillar for the definition and selection of the methodologies and activities to be included in the DEC plan, which will be prepared by the WP6 leading team and reviewed and approved by the Consortium Committee. This project data will be publish in open access scientific journals.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.pyrapreg.org/ 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