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.: PACTR202108825067735 Date of Approval: 23/08/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title CASPER study
Official scientific title Calcium Aspirin Preeclampsia/ Eclampsia Early Prevention and Response Study
Brief summary describing the background and objectives of the trial Globally, preeclampsia/ eclampsia remains the third leading cause of maternal mortality. In developing countries, the burden of preeclampsia/eclampsia is worsened by lack of preventive interventions which have been identified to be sophisticated, expensive but effective in early detection of its risk. As a result, there is still more gaps in what could be feasibly work for developing countries. Currently Malawi has not been spared out to this high incidence of preeclampsia/ eclampsia which has highly affected perinatal outcomes and contributed more to an increase in maternal mortality ratio. Despite WHO recommending administration of low dose aspirin or calcium as a preventive measure, literature has not been found regarding its use in the Malawian hospital set up. There are still some gaps in knowledge as what could be the barrier to early pregnancy intervention and also the feasibility and effectiveness of low dose aspirin given together with calcium in preventing preeclampsia/ eclampsia in Malawian setting. MAIN OBJECTIVE: To assess barriers to early pregnancy intervention and the effectiveness of low dose of aspirin and calcium in preventing preeclampsia in Blantyre, Malawi. Specifically,Phase one will assess health worker/ policy makers barriers to providing early pregnancy intervention ( eg calcium/aspirin) to prevent preeclampsia/eclampsia to high risk pregnant women. It will also investigate patient’s barriers to accessing early pregnancy intervention to prevent preeclampsia/eclampsia among women who had suffered from preeclampsia/ eclampsia at QECH Blantyre, Malawi. Phase two will mainly focus on assessing the efficacy of early low dose of aspirin and calcium in preventing preeclampsia and eclampsia in a randomised clinical trial in Blantyre, Malawi and identify challenges of early use of low dose aspirin and calcium in high risk pregnant women in Blantyre, Malawi.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CASPER
Disease(s) or condition(s) being studied Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 26/09/2021
Actual trial start date 29/11/2021
Anticipated date of last follow up 30/09/2022
Actual Last follow-up date 10/08/2023
Anticipated target sample size (number of participants) 296
Actual target sample size (number of participants) 300
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
3118 College Of Medicine Research Ethics Committe
PMRACTRCIV1812202 Pharmacy Medicines Regulatory Authority of Malawi
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 Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Low dose of aspirin 150mg once daily for aspirin versus placebo 1gram calcium once daily to all participants From 12 weeks to 34 weeks gestation The women will be randomized to treatment or placebo depending on which one of the four health centre ( cluster randomisation) at which they were first seen. They will be screened and enrolled between 11 to 16 weeks and aspirin/placebo, and calcium will be provided.On the initial visits, participants will be given general health education on prevention of preeclampsia. Thereafter, pre packed bottles/ packets in order of enrollment will be dispensed. The women will be asked to keep their supplies at room temperature and instructions to take one tablet of each supply in the evening daily, approximately one hour after meal will be given.Master log for the study products will be known by pharma nova company personnel who will be responsible for production and blinding of study products. This information will be shared to pharmacist of record from John Hopkins who will be responsible for storage and dispensing of study products to the necessary sites. Since we are using cluster randomization, the study products will be dispensed based on the cluster one is in and not individually allocating products.Both participants, care givers and investigators will be masked. Aspirin and placebo will be packed in identical bottles/boxes of 4weeks supply. The placebo and intervention tablets will have similar taste and appearance 148
Control Group Placebo Placebo 150 mg once daily from between 12 to 16 weeks to 34 weeks gestation calcium 1 gram once daily between 12 to 16 weeks up to 34 weeks gestation From 12 -16 to 34 weeks gestation ( 18 -22 weeks) The women will be randomized to treatment or placebo depending on which one of the four health centre (cluster randomisation) at which they were first seen. They will be screened and enrolled between 11 to 16 weeks and aspirin/placebo, and calcium will be provided.On the initial visits, participants will be given general health education on prevention of preeclampsia. Thereafter, pre packed bottles/ packets in order of enrollment will be dispensed. The women will be asked to keep their supplies at room temperature and instructions to take one tablet of each supply in the evening daily, approximately one hour after meal will be given.Master log for the study products will be known by pharma nova company personnel who will be responsible for production and blinding of study products. This information will be shared to pharmacist of record from John Hopkins who will be responsible for storage and dispensing of study products to the necessary sites. Since we are using cluster randomization, the study products will be dispensed based on the cluster one is in and not individually allocating products.Both participants, care givers and investigators will be masked. Aspirin and placebo will be packed in identical bottles/boxes of 4weeks supply. The placebo and intervention tablets will have similar taste and appearance. 148 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1 All urban health centres providing maternal health services in Blantyre 2 All Pregnant women screened and identified to be at risk of preeclampsia/ eclampsia such as those with: Hypertensive disease during previous pregnancy Chronic kidney disease Type 1&2 diabetes Chronic hypertension Auto immune disease such as systematic lupus erythematosus or antiphospholipid syndrome previous history of preeclampsia/eclampsia, previous an explained abruption advanced maternal/extreme of age, teenagers 3. Those with family history of eclampsia/preeclampsia, twin pregnancy, chronic hypertension, diabetes ) 4. They should be between 11 to 16 weeks gestation 1. All women with increased risk of bleeding due to coagulation disorders or placenta previa 2. Women who are allergic to aspirin or calcium 3. Women who are planning to deliver at another health facility 4. All women who did not consent Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 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 02/08/2021 Pharmacy Medicines Regulatory Authority of Malawi and College of Medicine Ethics committee
Ethics Committee Address
Street address City Postal code Country
1. Chilambula Road, P.O. Box 30241 Lilongwe 0000 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 16/10/2020 College Of Medicine Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Mahatma Ghandi Road Blantyre 360 Malawi
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome preeclampsia and or eclampsia At delivery and up to six weeks post delivery
Secondary Outcome Maternal mortality, placenta abruptio, admission to ICU, stroke, post partum haemorrhage, timing of delivery, gestational age at delivery, HELLP syndrome, near miss event, birth weight, admission in nursery ICU, intra uterine death, fresh still birth, small for gestational age or neonatal respiratory support. At delivery and 6 weeks post partum
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Blantyre District Hospital health centres Chichiri Blantyre 66 Malawi
Queen Elizabeth Central Hospital Chichiri Blantyre 95 Malawi
FUNDING SOURCES
Name of source Street address City Postal code Country
Scholarship Narellan Road, Campbelltown Sydney 2560 Australia
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Preeclampsia Research Laboratories PEARLS Heart Research Institute 7 Eliza Street, Newtown NSW Sydney 2042 Australia Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
College of Medicine Mahatmaghandi Road, Chichiri Blantyre 360 Malawi
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Memory Moque moque87@gmail.com +265993742326 Mahatma Ghand Road
City Postal code Country Position/Affiliation
Blantyre 360 Malawi PhD student
Role Name Email Phone Street address
Public Enquiries Eric Umar eumar@medcol.mw 00265888118993 Mahatma Ghandi Road, Chichiri
City Postal code Country Position/Affiliation
Blantyre 360 Malawi COMREC chair
Role Name Email Phone Street address
Scientific Enquiries Luis Gadama lgadama@medcol.mw +265991042320 Mahatma Ghandi Road, chichiri
City Postal code Country Position/Affiliation
Blantyre 360 Malawi PhD supervisor
Role Name Email Phone Street address
Scientific Enquiries Annemarie Hennessy an.hennessy@westernsydney.edu.au +61246203618 Narellan Road, Campbelltown
City Postal code Country Position/Affiliation
Sydney 2560 Australia Primary Supervisor
Role Name Email Phone Street address
Scientific Enquiries Angela Makris Angela.Makris@health.nsw.gov.au +61402494758 Liverpool Hospital Elizabeth Drive Liverpol NNSW
City Postal code Country Position/Affiliation
Sydney 2170 Australia PhD Supervisor
Role Name Email Phone Street address
Scientific Enquiries Renuka Shanmugalingam Renuka.Shanmugalingam@health.nsw.gov.au +61421744353 Liverpool Hospital , Elizabeth Drive
City Postal code Country Position/Affiliation
Sydney 2170 Australia PhD supervisor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The documents which will be made available would include study protocol, statistical analysis plan, informed consent forms at the beginning 9 months and ending 36 months following article publication. This will be made available by investigators whose proposed use of the data has been approved by an independent review committee (“learned intermediary”) identified for this purpose. This data will also be shared according to COMREC and WSU regulations. The data will be made available for individual participant metaanalysis. The proposal may be submitted up to 36 months following article publication. After 36 months the data will be available in out University’s data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing date may be found at grs.hdr@westernsydney.edu.au Summary results will be made available within 12 months of the study completion date on a cloud de identified link Informed Consent Form,Statistical Analysis Plan,Study Protocol Summary results will be made available within 12 months of the study completion date on a cloud based de identified link. This will be between October 2022 to October 2023 Open access to de identified data. Data will shared after request to the Principal Investigator, supervisors, COMREC or WSU.
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