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.: PACTR201103000280319 Date of Approval: 14/03/2011
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Scheduled screening versus preventative treatment for the control of malaria in pregnancy in Malawi: a randomised controlled trial
Official scientific title Scheduled intermittent screening and treatment in pregnancy (ISTp) versus intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) in women protected by insecticide treated nets (ITNs) for the control of malaria in pregnancy in Malawi: a randomized controlled trial
Brief summary describing the background and objectives of the trial 3-year, open-label two-arm multicentre individually randomised controlled superiority trial conducted in area with high SP resistance in southern Malawi comparing the efficacy, safety and cost-effectiveness of intermittent preventive therapy with SP (IPTp-SP) with a new strategy consisting of intermittent screening and treatment in pregnancy with rapid diagnostic tests and treatment with RDT positive women with DHA-piperaquine (DP) (ISTp-DP). Sample size is 1,656
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ISTp Trial
Disease(s) or condition(s) being studied Infections and Infestations,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention
Anticipated trial start date 01/05/2011
Actual trial start date 28/07/2011
Anticipated date of last follow up 01/11/2013
Actual Last follow-up date 14/10/2013
Anticipated target sample size (number of participants) 1656
Actual target sample size (number of participants) 1872
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
ISRCTN69800930 Current Controlled Trials
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 Permuted block randomisation with varying block size, computer generated. 1656 women will be randomized; including 1156 primi- and secundigravidae (G1-2) and 500 multigraidae (g3+) in sealed opaque envelopes Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomisation with varying block size, computer generated. 1656 women will be randomized; including 1156 primi- and secundigravidae (G1-2) and 500 multigraidae (g3+) in sealed opaque envelopes Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomisation with varying block size, computer generated. 1656 women will be randomized; including 1156 primi- and secundigravidae (G1-2) and 500 multigraidae (g3+) in sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group IPTp 3 tablets stat, 3 or 4 times during pregnancy Stat course (single dose) IPTp-SP: 3 to 4 doses of IPTp with SP as part of FANC (according to current practice in Malawi women coming early get 4 doses, women coming from 24 weeks get 3 doses of SP) 936 Active-Treatment of Control Group
Experimental Group ISTp-DP RDT + women treated with 3 days DHA-PQ. dosage being 2 mg/kg/day of dihydroartemisinin and 16 mg/kg/day piperaquine. 3 or 4 screening events Screening for malaria using a combined HRP-2/ pLDH (P. falciparum/ pan-malaria) rapid diagnostic test (First Response® Malaria pLDH/HRP2 Combo Test, target antigen pLDH (pan); HRP2; Premier Medical Corporation Ltd, USA), and treatment if RDT-positive with dihydroartemisinin-piperaquine (Sigma Tau). Each tablet will contain 40 mg dihydroartemisinin and 320 mg piperaquine. 936
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Viable singleton pregnancy 2. Gestational age 16 to 28 weeks (inclusive) by LMP (if available) or fundal height 3. No history of IPTp use during this pregnancy 4. Willing to participate and complete the study schedule 5. Has provided written informed consent 6. Resident of study area and intending to stay in the area for the duration of the follow-up 7. Willing to deliver in the labour ward of the study clinic or hospital 1. HIV positive or unknown HIV status 2. Multiple gestations 3. High risk pregnancy resulting in referral to tertiary delivery facilities according to local guidelines, these include: a. Age under 16 or over 40 b. Five or more previous pregnancies c. Pre-existing illness likely to cause complication of pregnancy (hypertension, diabetes, asthma, epilepsy, renal disease, fistula repair, leg or spine deformity) d. Two or more previous miscarriages or induced abortions e. Previous caesarian section delivery, vacuum extraction or symphysiotomy f. History of pregnancy or birth complications (pre-eclampsia or post-partum haemorrhage) 4. Severe anaemia requiring blood transfusion (Hb ¿ 7.0 g/dL) at enrolment 5. Known allergy or previous adverse reaction to any of the study drugs 6. Unable to give informed consent (for example due to mental disability) 7. Previous inclusion in the same study 16 Year(s) 40 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 28/02/2011 Research Ethics Committe, Liverpool School of Tropical Medicine
Ethics Committee Address
Street address City Postal code Country
Pembroke Place Liverpool l35qa United Kingdom
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 26/03/2010 COMREC, College of Medicine Research Ethics Comittee
Ethics Committee Address
Street address City Postal code Country
Mahatma Gandhi Road Private Bag 360. Chichi Blantyre 3, Malawi Blantyre 3 Private bag 360 Malawi
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 25/07/2011 NATIONAL HEALTH SCIENCES RESEARCH COMMITTEE
Ethics Committee Address
Street address City Postal code Country
Ministry of Health, Capital Hill Lilongwe P.O. BOX 30377 Malawi
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Secondary Outcome Placental malaria (any species) a. past infection (histopathology) b. Active infection(detected by histopathology, microscopy, rapid diagnotic test or PCR)
Secondary Outcome Maternal malaria infection (peripheral blood) At delivery detected by a. Microscopy; b. RDT; c. PCR
Secondary Outcome Peripheral malaria infection during pregnancy, detected by microscopy or PCR
Secondary Outcome Birth Weight mean birth weight (grams) low birth weight (less than 2,500 g)
Secondary Outcome Gestational age mean gestational age at birth (grams) Pre-term birth (less than 37 weeks)
Secondary Outcome Small for gestational age at birth
Secondary Outcome Maternal haemoglobin and anaemia At delivery (mean maternal g/dL; anaemia where HB less than or equal to 11 g/dL; moderate to severe anaemia where Hb is less than or equal to 8 g/dL)
Secondary Outcome Miscarriage loss of foetus before 28 weeks gestation
Secondary Outcome Stillbirth birth at 28 weeks or later showing no signs of life
Secondary Outcome Composite endpoint of primary endpoint plus fetal loss miscarriage or stillbirths
Secondary Outcome Infant Death 1. perinatal death (stillbirth or death within 7 days of birth) 2. neonatal death (death within 28 days of birth)
Secondary Outcome Malaria infection of the newborn detected by analysis of umbilical cord blood with a. RDT b. Microscopy c. PCR
Secondary Outcome Foetal haemoglobin and anaemia Sampling of umbilical cord blood at birth a. mean foetal haemoglobin (g/dL) b. Foetal anaemia (Hb less than or equal to 12.5 g/dL) c. moderate to severe foetal anaemia
Secondary Outcome Incidence of documented clinical malaria episodes during second and third trimester of pregnancy (history of fever in last 24 hours and documented malaria microscopy or RDT positive)
Secondary Outcome Presence of any evidence of malaria infection at term Last antenatal visit - identified through microscopy, PCR Or at delivery id through periperal and placental RDT, microscopy, PCR or placental histopathology (active or past)
Secondary Outcome Incidence of other illness episodes Apparent at scheduled antenatal clinical visits or resulting in unscheduled clinic visits
Secondary Outcome Incidence and prevalence of clinical malaria in infants by seven days and six to eight weeks (determined by RDT, microscopy, PCR)
Secondary Outcome Prevalence of symptomatic infant anaemia at seven days and six to eight weeks a. anaemia b. moderate to severe anaemia
Secondary Outcome Incidence of other illness episodes in infants apparent at scheduled postnatal clinic visits or resulting in unscheduled postnatal clinic visits
Secondary Outcome SAFETY: severe cutaneous skin reaction in mothers within 30 days of drug intake
Secondary Outcome SAFETY: other serious adverse events in mothers
Secondary Outcome SAFETY: Congenital malformation identified by six weeks after birth
Secondary Outcome SAFETY: Neonatal jaundice within 24 hours and at seven days
Secondary Outcome SAFETY: Lab test results outside of normal range
Secondary Outcome Tolerability outcomes 1. non-serious adverse events in mothers 2. adherence to study medication
Secondary Outcome Immunology outcome Concentration of antibodies known to be associated with protection against malaria in pregnancy and general Including antibodies recognizing variant surface antigens on P. falciparum infected erythrocytes that block parasite adhesion to chondroitin sulphate
Primary Outcome 1. In women in their first or second pregnancy (G1-2): Small for gestational age, LBW or preterm birth G1-2: composite endpoint measured at delivery
Primary Outcome 2. Multigravidae (G3+): Malaria infection at term and delivery G3+: Malaria infection at term and delivery, defined as evidence of current or recent infection assessed at delivery by placental histopathology (¿active¿ or ¿past¿ infection) or RDT (pLDH or HRP2 positive, any species) or PCR positive (any species).
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
College of Medicine (CoM), Blantyre, Malawi Mahatma Gandhi Road Blantyre P/Bag 360 Blantyre Malawi
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP P.O. Box 93015, Laan van Nieuw Oost Indië 334 The Hague 2509 AA Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Prof Linda Kalilani College of Medicine, Mahatma Gandhi Road Blantyre P/Bag 360 Blantyre Malawi
Dr Doreen Ali National Malaria Control Programme, MoH, Malawi Lilongwe Malawi
Dr Brian Faragher LSTM, Pembroke Place Liverpool L3 5QA United Kingdom
Dr Mwayiwawo Madanitsa College of Medicine, Mahatma Gandhi Road Blantyre P/Bag 360 Blantyre Malawi
Prof Feiko ter Kuile LSTM, Pembroke Place Liverpool L3 5QA United Kingdom
Dr Stephen Rogerson University of Melbourne Melbourne Vic. 305 Australia
Dr Annamieke van Eijk LSTM, Pembroke Place Liverpool L3 5QA United Kingdom
Dr Victor Mwapasa College of Medicine, Mahatma Gandhi Road Blantyre P/Bag 360 Blantyre Malawi
Dr Annamieke van Eijk LSTM, Pembroke Place Liverpool L3 5QA United Kingdom
Dr Victor Mwapasa College of Medicine, Mahatma Gandhi Road Blantyre P/Bag 360 Blantyre Malawi
Prof Steve Meshnick University of North Carolina North Carolina NC 28403 United States of America
Dr Steve Taylor University of North Carolina North Carolina NC 28403 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Feiko ter Kuile terkuile@liv.ac.uk +44 151705 3287 School of Tropical Medicine Pembroke Place
City Postal code Country Position/Affiliation
Liverpool L3 5QA United Kingdom Tropical Epidemiology, Child and Reproductive Health Group, LSTM
Role Name Email Phone Street address
Public Enquiries Linda Kalilani lkalilani@medcol.mw +265-888783427 Mahatma Gandhi Road Private Bag 360. Chichi Blantyre 3, Malawi
City Postal code Country Position/Affiliation
Blantyre Private Bag 360 Malawi Community Health, College of Medicine, Blantyre
Role Name Email Phone Street address
Scientific Enquiries Feiko ter Kuile terkuile@liv.ac.uk +44 151705 3287 School of Tropical Medicine Pembroke Place
City Postal code Country Position/Affiliation
Liverpool L3 5QA United Kingdom
REPORTING
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