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.: PACTR202001787519553 Date of Approval: 14/01/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Low dose aspirin for preventing intrauterine growth restriction and preeclampsia in sickle cell pregnancy (PIP-SICKLE): a randomised controlled trial.
Official scientific title Low dose aspirin for preventing intrauterine growth restriction and preeclampsia in sickle cell pregnancy (PIP-SICKLE): a randomised controlled trial.
Brief summary describing the background and objectives of the trial Background and significance: Sickle cell disease (SCD) is a haemoglobinopathy fraught with complications as a result of vaso-occlusion, thrombosis and chronic anaemia. Pregnancy in sickle cell disease aggravates already existing pathophysiological mechanisms in affected women. It worsens anaemia and the resultant chronic hypoxia, increases the risk of infections, worsens vasoconstriction and alters procoagulation mechanisms. As a result, sickle cell pregnancies are often complicated by preeclampsia, stillbirths, preterm deliveries, intrauterine growth restriction (IUGR), and an increase in their usual crises and chest infections. Women with sickle cell disease therefore have a high incidence of maternal and perinatal morbidity and mortality. In the general population, low dose aspirin is known to decrease the risk of cardiovascular events and to prevent platelet clumping thus enhancing free flow of erythrocytes. In a previous study we found a reversal in prostacyclin-thromboxane ratio in pregnant SCD women, a situation that is also found in non-sickle pregnancies with preeclampsia and unexplained IUGR (1). Low dose aspirin (LDA) has been found to reduce the incidence of pre-eclampsia and IUGR in high-risk women due to its reduction of vasoconstrictor thromboxane whilst sparing prostacyclin, in effect correcting the ratio (2). It has been found to be safe and is used extensively in pregnancy (2) but has not been tested specifically in sickle cell pregnancy. We hypothesize that LDA would reduce the incidence of IUGR and preeclampsia in pregnant SCD women. Objectives are: 1. To determine effect of LDA use during pregnancy in HbSS and HbSC women on risk of IUGR, perinatal death or miscarriage 2. To determine effect of LDA use during pregnancy in HbSS and HbSC women on risk of maternal complications including preeclampsia, preterm delivery, number of vaso-occlusive crises, etc 3. To build capacity in conducting RCTs
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PIPSICKLE
Disease(s) or condition(s) being studied Genetic Diseases,Haematological Disorders,Obstetrics and Gynecology,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied Intrauterine growth restriction, preeclampsia
Purpose of the trial Prevention
Anticipated trial start date 02/01/2020
Actual trial start date 29/06/2020
Anticipated date of last follow up 01/10/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 476
Actual target sample size (number of participants)
Recruitment status Recruiting
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 Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Sealed opaque envelopes 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 Aspirin 100mg The drugs will be started from 12 – 16 weeks gestation and continued till 36 weeks or delivery, whichever comes earlier. Those in the LDA group will receive 100mg aspirin daily taken at once just before bedtime while those in the placebo group will receive a tablet that looks like the active drug in terms of size and thickness. Several doses of aspirin have been used for prophylaxis and meta-analyses have reported a dose dependent effect (Duley, Roberge). A recent randomized controlled trial on the prevention of preterm preeclampsia in high risk women used a dose of 150mg daily without significant adverse effect. As pregnant women with sickle cell disorder have a lower BMI than other pregnant women (ref), we propose to use a dose of 100mg, which falls well within the range of 50 – 150 mg that has been used in many studies. The drugs will be started from 12 – 16 weeks gestation and continued till 36 weeks or delivery, whichever comes earlier. The tablets will be prepared in sachets and dispensed in 2 weekly doses although an extra sachet will be included in each pack in case of loss of tablets. The women will be sent daily reminders by text message, questioned on compliance each visit and asked to bring in their used sachets for sighting. Randomisation will be done by computer generated numbers, which will be sealed into opaque envelopes that are consecutively numbered. Women will be randomized with the use of a web- based randomization software known as ‘Sealed envelope’ in a 1:1 ratio in blocks stratified according to centre. Only one of the researchers will be aware of the actual codes and she will not be in contact with any of the study participants. 238
Control Group Placebo 0mg The placebo will be started from 12 – 16 weeks gestation and continued till 36 weeks or delivery, whichever comes earlier. Those in the LDA group will receive 100mg aspirin daily taken at once just before bedtime while those in the placebo group will receive a tablet that looks like the active drug in terms of size and thickness. Several doses of aspirin have been used for prophylaxis and meta-analyses have reported a dose dependent effect (Duley, Roberge). A recent randomized controlled trial on the prevention of preterm preeclampsia in high risk women used a dose of 150mg daily without significant adverse effect. As pregnant women with sickle cell disorder have a lower BMI than other pregnant women (ref), we propose to use a dose of 100mg, which falls well within the range of 50 – 150 mg that has been used in many studies. The drugs will be started from 12 – 16 weeks gestation and continued till 36 weeks or delivery, whichever comes earlier. The tablets will be prepared in sachets and dispensed in 2 weekly doses although an extra sachet will be included in each pack in case of loss of tablets. The women will be sent daily reminders by text message, questioned on compliance each visit and asked to bring in their used sachets for sighting. Randomisation will be done by computer generated numbers, which will be sealed into opaque envelopes that are consecutively numbered. Women will be randomized with the use of a web- based randomization software known as ‘Sealed envelope’ in a 1:1 ratio in blocks stratified according to centre. Only one of the researchers will be aware of the actual codes and she will not be in contact with any of the study participants. 238 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Age 18 years and above Singleton fetus Women with sickle cell anaemia i.e. Haemoglobin SS. 16 weeks gestation or less at recruitment, confirmed by an ultrasound scan or certain last menstrual period dates Other sickle cell disease variants eg Hb SC Women with associated medical conditions in pregnancy eg HIV infection, diabetes mellitus, chronic hypertension, renal disease, sickle nephropathy Women with multiple pregnancy Hypersensitivity to aspirin History of vaso-occlusive crisis in the last 4 weeks History of blood transfusion in the last 3 months Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 49 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 19/11/2019 Lagos University Teaching Hospital Health Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Idi-Araba Surulere 101283 Nigeria
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 02/12/2019 Federal Medical Centre
Ethics Committee Address
Street address City Postal code Country
Railway Compound Ebute-Metta Lagos 1097 Nigeria
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 29/11/2019 Lagos State Government
Ethics Committee Address
Street address City Postal code Country
1 Garniu Street Lagos Island Lagos 00000 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome intrauterine growth restriction, birth weight below the 10th centile for gestational age on INTERGROWTH 21 birthweight charts, or stillbirth, or fetal death or miscarriage at the end of pregnancy
Secondary Outcome preeclampsia from 20 weeks gestational age
Secondary Outcome maternal death, preterm delivery, number of crises, need for blood transfusion at the end of pregnancy
Secondary Outcome Complications such as - Urinary tract infection - Lower Respiratory tract infection - Acute chest syndrome - Retained placenta - Placental abruption at the end of pregnancy
Secondary Outcome Potential adverse effects such as - Vaginal bleeding - Epigastric pain - Heartburn at the end of pregnancy
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Lagos University Teaching Hospital Idi-Araba Surulere 101283 Nigeria
Lagos State University Teaching Hospital Oba Akinjobi street Ikeja 100282 Nigeria
Island Maternity Hospital Broad street Lagos Island 100001 Nigeria
Alimosho General Hospital Lasu-Igando Road Igando 100267 Nigeria
Randle General Hospital Randle Road Surulere 101283 Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
TETfund National Research Fund N0 6 Zambezi Crescent, Off Aguiyi Ironsi Street, Maitama, Abuja, FCT Nigeria Abuja FCT 900271 Nigeria
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor TETFUND Abuja Abuja Nigeria Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Ochuwa Babah Idi-Araba Surulere 101283 Nigeria
Titilope Adeyemo Idi-Araba Surulere 101283 Nigeria
Chinyere Ezeaka Idi-Araba Surulere 101283 Nigeria
Oluwakemi Odukoya Idi-Araba Surulere 101283 Nigeria
Obiyo Nwaiwu Idi-Araba Surulere 101283 Nigeria
Dr Yusuf Oshodi Oba Akinjobi Way Ikeja 100271 Nigeria
Prof Babatunde Ogunnaike Newark Delaware 19716311 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Bosede Afolabi bosedeafolabi2003@yahoo.com +2348023154964 Idi-Araba
City Postal code Country Position/Affiliation
Surulere 101283 Nigeria Professor and Head of Department of Obstetrics and Gyynaecology College of Medicine of University of Lagos and Lagos University Teaching Hospital Idi Araba Lagos Nigeria
Role Name Email Phone Street address
Public Enquiries Ochuwa Babah ochuwab@yahoo.co.uk +2348023591137 Idi-Araba
City Postal code Country Position/Affiliation
Surulere 101283 Nigeria Lecturer and Consultant Obstetrician and Gynaecologist Ultrasound and Fetal Medicine Unit College of Medicine of University of Lagos and Lagos University teaching Hospital Idi Araba Lagos
Role Name Email Phone Street address
Scientific Enquiries Bosede Afolabi bosedeafolabi2003@yahoo.com +2348023154964 Idi-Araba
City Postal code Country Position/Affiliation
Surulere Lagos 101283 Nigeria Professor and Head of Department of Obstetrics and Gyynaecology College of Medicine of University of lagos and Lagos University teaching Hospital Idi Araba Lagos Nigeria
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We will store the data and deposit it in ‘Open Science Framework’, after approval is obtained from the ethics committee. We will also provide metadata along with the data to describe it. Most of these data will have value to other research users but we will not share the identifying personal biodata such as home address, phone numbers or occupation. 1. Suitability for sharing We believe that our data is suitable for sharing as we will not be sharing any data with known identifiers. 2. Discovery by potential users of the research data Potential new users may find out about our data including the metadata on the ‘Open Science Framework’. We will share the data at the time of publication of our first paper. We will share the assigned DOI number, the OSF website details and our approach to data sharing as an appendix to our publications to aid accessibility. We will also share these at any conference presentations and our study website, as well as local meetings and conferences of our society of Obstetrics and Gynaecology. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol 2 years 1. Governance of access The principal investigator will bear overall responsibility for this data and will be responsible for deciding whether to supply research data to a potential new user. The CMUL HREC will provide an independent oversight function. 2. The study team’s exclusive use of the data Data will be made available at the time of publication, at the latest. Depending on the nature of the data itself, data may be made available earlier, either on an individual basis to interested researchers and/or potential new collaborators. 3. Restrictions or delays to sharing, with planned actions to limit such restrictions We will ensure that our informed consent forms clearly spell out and seek consent for future data sharing. 4. Regulation of responsibilities of users All external users will sign and be bound by our data sharing agreements and will not be allowed to use the data for reasons other than stated in their application.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
unavailable 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