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.: PACTR201905721140808 Date of Approval: 20/05/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Intermittent Presumptive Treatment in Pregnancy With Sulfadoxine-Pyrimethamine using Rapid Diagnostic Test Screening And Treatment at First Antenatal Care Visit
Official scientific title Safety and Efficacy of Intermittent Presumptive Treatment in Pregnancy With Sulfadoxine-Pyrimethamine using Rapid Diagnostic Test Screening And Treatment at First Antenatal Care Visit
Brief summary describing the background and objectives of the trial Intermittent Preventive Treatment in Pregnancy (IPTp) with Sulfadoxine-Pyrimethamine (SP) is recommended in moderate to high transmission areas of sub-Saharan Africa. However IPTp with SP (IPTp-SP) efficacy is threatened by the ever increasing parasite resistance to SP. The continued use of SP for IPTp would result in further reduction of IPTp-SP efficacy and completely compromise its effectiveness at preventing malaria in pregnancy (MIP) associated adverse outcomes. This constitutes a serious threat for mothers and their offspring’s in sub-Saharan Africa. Reducing SP interaction with the already mutated parasite would prevent further selection of mutated parasites, reduce SP resistance and improve IPTp-SP efficacy. This can be achieved by introducing at first Antenatal (ANC) visit, malaria Rapid Diagnostic Testing (RDT) and treatment of positive mothers with a safe and fully effective anti-malarial drug before they are administered with SP during subsequent ANC visits; while mothers testing negative by RDT receive SP at first and during following ANC visits; a package labeled as IPTp-SP+ henceforth. We therefore plan to conduct a clinical trial that will compare the current standard of care IPTp-SP with IPTp-SP+ in terms of their efficacy at clearing peripheral maternal and placental parasitemia and at preventing adverse outcomes associated with malaria in pregnancy. Volunteer HIV non-infected and eligible mothers will be recruited. Relevant socio-demographic and clinical information will be obtained and blood samples will be taken for Hemoglobin (Hb) and malaria molecular testing at enrollment; days 14, 28, 35, 42 and 63 and at delivery. Blood samples for pharmacokinetics’ testing will also be collected on days 0, 14, 28, 35 and 42 from mothers in the IPTp-SP+ testing positive by RDT at first ANC visit. At delivery, babies’ blood (peripheral and cord) and placental samples will be collected. Babies will be followed up to one year after delivery.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) IPTpSP Plus
Disease(s) or condition(s) being studied Infections and Infestations,Neonatal Diseases,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention
Anticipated trial start date 22/04/2019
Actual trial start date
Anticipated date of last follow up 31/10/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 392
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
TDRC STC 2018 8 Tropical Diseases Research Centre Scientific and Technical Committees
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 Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group IPTpSP Sulfadoxine-Pyrimethamine (SP) 500/25 mg One day monthly for 3 month Mothers in the IPTp-SP group will receive 3 doses of SP at enrollment, day 35 and day 63. Thereafter SP monthly until delivery. 196 Active-Treatment of Control Group
Experimental Group IPTpSP Plus Dihydroartemisinin-Piperaquine (DP) 40/320 mg once daily and/or Sulfadoxine-Pyrimethamine (SP) 500/25 mg once daily. DP for 3 days then SP once daily for 2 months given 4-6 weeks apart or SP once daily for 3 months given 4-6 weeks apart Mothers in IPTp-SP+ group will be tested with RDT at first ANC visit; If they test positive they will be treated with DP followed with 2 doses of SP given at days 35 and 63; if negative they will be given three doses of SP at enrollment, days 35 and 63. Thereafter SP monthly until delivery. 196
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Gestational age of 16 to 24 weeks at enrolment; • Asymptomatic* on presentation • Hb ≥ 7 g/dL; • HIV negative at enrolment • No history of IPTp-SP or antimalarial drug use during the current pregnancy • At least 15 years old; • Residence within the health facility catchment’s area; • Willing to deliver at the health facility; • Willing to adhere to the study requirements (HIV voluntary counselling and testing (VCT included); • 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 (An assent will also be obtained from the participant). Asymptomatic defined as absence of fever (temperature <37.5 °C) at baseline; less than three of the following symptoms: fever in the past 24 h, weakness/fatigue; muscle and/or joint aches, headache • HIV positive or unknown at enrolment • Hb<7 g/dl • History of allergic reactions to the study drugs; • History of known pregnancy complications or bad obstetric history including pre-existing illness likely to cause complication of pregnancy such as repeated abortions, stillbirths or eclampsia; • History or presence of major illnesses likely to influence pregnancy outcome including hypertension, diabetes mellitus, asthma, epilepsy, renal disease, liver disease, fistula repair, heart disease, or active tuberculosis; • Current cotrimoxazole prophylaxis or ARV treatment; • Any significant illness at the time of screening that requires hospitalization, including severe malaria; • Intent to move out of the study catchment area before delivery or deliver at relative’s home out of the catchment area. • Prior enrolment in the study or concurrent enrolment in another study. • Unable to take oral medication • Clear evidence of recent (2 weeks) treatment with antimicrobials with antimalarial activity (clindamycin, azithromycin, clarithromycin, levofloxacin etc.); • On at least one of the following drugs: Pentamidine, Antiarrhythmic agents (e.g. amiodarone, sotalol), Antihistamines (e.g. promethazine), Antifungals (systemic): ketoconazole, fluconazole, itraconazole, Diuretics (e.g. hydrochlorothiazide, furosemide), Antipsychotics (neuroleptics): haloperidol, thioridazine, Antidepressants: imipramine, citalopram, escitalopram, Antiemetics: domperidone, chlorpromazine, ondansetron Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 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 29/03/2019 National Health Research Ethics Board
Ethics Committee Address
Street address City Postal code Country
Paediatric Centre of excellence, University Teaching Hospital Lusaka 10101 Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • Relative hazard of P. falciparum infection diagnosed by PCR at day 42 after randomization • Medication-related adverse events and serious adverse events until 1-year post-partum Days 42
Secondary Outcome • Proportion with treatment or prevention failure at day 42 stratified according to study drug (SP or DP); • Relative hazard of P. falciparum infection diagnosed by PCR or microscopy at days 14, 28, 35, 42, 63, delivery, and 1-month post-partum in infants; • Proportion who experience at least one episode of P. falciparum infection by day 14, 28, 35, 42, or 63; • Median time to first episode of malaria in pregnancy; • Acute, chronic, and prior placental infection at delivery; • Mean birth weight and prevalence of low birth weight (within 72 hours post-partum); • Neonatal mortality (within 28 days post-partum); • Congenital malaria diagnosed by PCR, placental malaria diagnosed by histopathology using placental biopsies; • Maternal anemia (hemoglobin changes at days 14, 28, 42 and 63); • Congenital anemia; • Incidences of pregnancy losses; • Congenital P. falciparum infection; • Relative allele frequencies of genotypic markers of drug resistance in malaria parasites; • Terminal elimination half-life of piperaquine determined by noncompartmental analysis of drug concentrations at 0, 14, 28, 35 and 42 days; Days 14, 28, 35, 42, 63, delivery and 1 year post delivery
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kashikishi Rural Health Centre Mutono Village Nchelenge 10101 Zambia
Nchelenge Urban Health Centre Kafimbwa Village Nchelenge 10101 Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical trial Partnership ANNA VAN SAKSENLAAN THE HAGUE S GRAVENHAGE Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Tropical Diseases Research Centre Ndola Teaching Hospital Ndola 10101 Zambia Research Institution
COLLABORATORS
Name Street address City Postal code Country
Nchelenge District Health Office Nchelenge Boma Nchelenge 10101 Zambia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Jean Bertin Bukasa Kabuya jeanbertinkabuya@yahoo.com +260977338641 Ndola Teaching Hospital
City Postal code Country Position/Affiliation
Ndola Zambia Tropical Diseases Research Centre
Role Name Email Phone Street address
Scientific Enquiries Christine Manyando cmanyando@yahoo.com +260977771763 Ndola Teaching Hospital
City Postal code Country Position/Affiliation
Ndola Zambia Tropical Diseases Research Centre
Role Name Email Phone Street address
Public Enquiries Sebastian Hachizovu hachizovus@tdrc.org.zm +260974223643 Ndola Teaching Hospital
City Postal code Country Position/Affiliation
Ndola Zambia Tropical Diseases Research Centre
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes A full analyzable de-identified data set Informed Consent Form,Statistical Analysis Plan,Study Protocol 6 months after peer reviewed publication Any author/s planning to do a secondary analysis will have to request from us through the sharing data site. The permission to share will be granted by the Tropical Diseases Research Centre directorate.
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