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.: PACTR201008000248160 Date of Approval:
Trial Status:
TRIAL DESCRIPTION
Public title Safe and Efficacious Artemisinin-based Combination Treatments for African Pregnant Women With Malaria
Official scientific title Safe and Efficacious Artemisinin-based Combination Treatments for African Pregnant Women With Malaria
Brief summary describing the background and objectives of the trial Malaria is responsible of high morbidity and mortality in resource-poor countries. Pregnant women, a high-risk group, are often excluded from clinical trials thus, the investigators lack sufficient information on the safety and efficacy of most antimalarials in pregnancy. The investigators propose to evaluate the efficacy and safety of 4 ACT(artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate and dihydroartemisinin-piperaquine), to treat pregnant women with P.falciparum malari
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Pregact
Disease(s) or condition(s) being studied Infections and Infestations,pregnancy,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/06/2010
Actual trial start date 11/06/2010
Anticipated date of last follow up 31/10/2014
Actual Last follow-up date
Anticipated target sample size (number of participants) 3480
Actual target sample size (number of participants) 3428
Recruitment status Completed
Publication URL http://www.nejm.org/doi/pdf/10.1056/NEJMoa1508606
Secondary Ids Issuing authority/Trial register
NCT00852423 clinicaltrials.gov
ITMP0308 Instritute of Tropical Medicine Belgium
NCT00852423 clinicaltrials.gov
ITMP0308 Instritute of Tropical Medicine Belgium
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 randomisation using a radomisation table created by a computer software program Sealed opaque envelopes Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised Simple randomisation using a radomisation 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
Control Group Artemether-lumefantrine 4 tablets of 20mg artemether/120mg lumefantrine twice a day 3 consecutive days AL (tablets containing FDC of 20mg artemether and 120 mg of lumefantrine) manufactured by Novartis, extensively used in Africa. AL registered in Switzerland in 1999, has since received marketing authorisation in several endemic and non-endemic countries and is WHO prequalified. 870 Active-Treatment of Control Group
Experimental Group Dihydroartemisinin(DHA)-piperaquine(PQ) 2 tablets of 40mg DHA/320mg PQ phosphate once a day 3 consecutive days DHA-PQ tablest are green film coated intentded for oral use and contain 20/160mg or 40/320 mg of DHA and PQ respectively. 40/320 mg for adults will be used. Developed by Sigma Tau in partnership with Medicines for Malaria Venture 870 Active-Treatment of Control Group
Experimental Group Artesunate(AS)-mefloquine(MQ) 2 tablets of 100mg AS/220 mg MQ once a day 3 consecutive days MQAS will be provided as a fixed-dose ACT. Two strengths (AS25+MQ55mg and AS100+MQ220mg) - dosing regimen calculated according to 12mg/kg AS and 24mg/kg MQ dose over three days. Pregnant women receive 2tablets/day for 3 days. Developed by Farmanguinhos with Drugs for Neglected Diseases Initiative. NB: if FDCs do not get WHO prequalification before recruitment separate AS & MQ will be used 870 Active-Treatment of Control Group
Control Group Artesunate-amodiaquine 2 tablets of 100 mg AS/270 mg AQ once a day 3 consecutive days AQAS developed by DNDi/Sanofi-Aventis prequalified by WHO in 2008. Avail. in several African countries, including trial countries. AQ-AS tablets are round, yellow one side, and white/slightly yellow other, AS engraved on one side and either 25, 50 or100 on other. Tablet in this trial will be 100mg/270mg AS/AQ, 100mg artesunate, 352.640mg of amodiaquine hydrochloride = 270mg of amodiaquine base 870 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 (women should not be included one week before the expected date of delivery) 2. P. falciparum monoinfection of any density, with or without symptoms 3. Hb >= 7 g/dL 4. At least 15 years old 5. Residence within the health facility cathment's area 6. willing to deliver at the health facility 7. willing to adhere to the study requirements (including, in Zambia and Malawi, HIV voluntary counseling and testing) 8. 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, also the minor woman will sign the consent form, to document that she is freely giving her assent to take part in the study) 1. history of allergic reactions to the study drugs 2. history of known pregnancy complications or bad obstretic history such as repeated stillbirht or eclampsia 3. history of presence of major ilnesses likely to influence the pregnancy outcome including diabetes mellitus, severe renal or heart disease, or active tuberculosis 4. current cotrimoxazole prohylaxis or ARV treatment 5. any significant illness at the time of screening that requires hospitalization, including severe malaria 6. intent to move out of the study cathment's area before delivery or deliver at relative's home out of the cathment's area 7. prior enrolment in the study or concurrent enrolment in another study 8. unable to take oral medication 9. clear evidence of recent (1 week) treatment with antimicrobials with antimalarial activity (clindamycin; azythromycin; etc.) 15 Year(s) 60 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 26/01/2009 Comite voor Medische ethiek, UZA
Ethics Committee Address
Street address City Postal code Country
Wilrijkstraat 10 Edegem 2610 Belgium
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Treatment failure (PCR adjusted) Day 63
Primary Outcome Safety profiles including significant changes in relevant laboratory values Until delivery
Secondary Outcome Time to failure Case by case
Secondary Outcome PCR unadjusted treatment failure Day 63
Secondary Outcome Gametocyte carriage (gametocyte - weeks) case by case
Secondary Outcome Asexual parasite clearance time Days to 2 consecutive negative blood slides
Secondary Outcome Gametocytaemia (prevalence and density) Day 7, 14, 21, 28, and 63 after treatment
Secondary Outcome Haemoglobin changes Day 14, 28, 42 and 63
Secondary Outcome The presence of acute, chronic or past infection of the placenta (prevalence) Delivery
Secondary Outcome Mean birth weight and prevlance of low birth weight newborns Delivery
Secondary Outcome In vitro and search of molecular markers related to drug resistance At time of the recurrent infection
Secondary Outcome Determination of the PK profile of MQ, AQ and PQ (on 120 women/treatment) Case by case
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
College of Medicine, University of Malawi; Chikwawa district hospital Blantyre Malawi
ISSR/Centre Muraz Nanoro and Nazoanga Burkina Faso
Kwame Nkrumah University of Science and Technology Kumasi Ejisu Sekyere East, Effiduase and Juaben Government Hospital, Ashanti Region Ghana
St. Paul's Mission Hospital Nchelenge, Nchelenge district, Luapula province Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP Hague
EDCTP Hague
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Institute of Tropical Medicine Nationalestraat 155 Antwerpen 2000 Belgium University
Primary Sponsor Institute of Tropical Medicine Nationalestraat 155 Antwerpen 2000 Belgium University
COLLABORATORS
Name Street address City Postal code Country
Theonest Mutabingwa, MD; National Institute for Medical Research PO Box 9653 Dar-es-Salaam Tanzania
Theonest Mutabingwa, MD; National Institute for Medical Research PO Box 9653 Dar-es-Salaam Tanzania
Tinto Halidou, PharmD; IRSS/Centre Muraz 01 BP 153 Bobo-Dioulasso Burkina Faso
Tinto Halidou, PharmD; IRSS/Centre Muraz 01 BP 153 Bobo-Dioulasso Burkina Faso
Theonest Mutabingwa MD; Seattle Institute for Biomedical and Clinical Research West Lake Avenue Seattle, Washington United States of America
Theonest Mutabingwa MD; Seattle Institute for Biomedical and Clinical Research West Lake Avenue Seattle, Washington United States of America
Dr. Harry Tagbor; Kwame Nkrumah University of Sciences and Technology UP Box 861 Kumasi Ghana
Dr. Harry Tagbor; Kwame Nkrumah University of Sciences and Technology UP Box 861 Kumasi Ghana
Dr. Linda Kalilani; University of Malawi, college of Medicine Private bag 360, Chichiri Blantyre 3 Malawi
Dr. Linda Kalilani; University of Malawi, college of Medicine Private bag 360, Chichiri Blantyre 3 Malawi
Dr. Michael Nambozi; Tropical Diseases Research Centre (TDRC) PO Box 71769 Ndola Zambia
Dr. Michael Nambozi; Tropical Diseases Research Centre (TDRC) PO Box 71769 Ndola Zambia
Dr H.D.F.H. Shallig; Institute of Tropical Medicine (KIT) Mauritskade 63 Amsterdam 1092 AD Netherlands
Dr H.D.F.H. Shallig; Institute of Tropical Medicine (KIT) Mauritskade 63 Amsterdam 1092 AD Netherlands
Prof Feiko Ter Kuile; Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA United Kingdom
Prof Feiko Ter Kuile; Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Umberto D'Alessandro udalessandro@itg.be 0032 3 2476354 Nationalestraat 155
City Postal code Country Position/Affiliation
Antwerpen 2000 Belgium Parasitology unit, parasite epidemiology and control
Role Name Email Phone Street address
Public Enquiries Umberto D'Alessandro udalessandro@itg.be 0032 3 2476354 Nationalestraat 155
City Postal code Country Position/Affiliation
Antwerpen 2000 Belgium Parasitology unit, parasite epidemiology and control
Role Name Email Phone Street address
Scientific Enquiries Umberto D'Alessandro udalessandro@itg.be 0032 3 2476354 Nationalestraat 155
City Postal code Country Position/Affiliation
Antwerpen 2000 Belgium Parasitology unit, parasite epidemiology and control
REPORTING
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