Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE)

NCT05253781 | Completed Phase 3 DMC

• 2 other identifiers: PACTR2020017875195532021-002867-23
• Study Type: interventional
• Target: 476
• Locations: 1 country
• Sites: 16

Brief Summary

Pregnancy in sickle cell disease (SCD) is fraught with many complications including preeclampsia (PE) and intrauterine growth restriction (IUGR). Previously, the investigators found an abnormality in prostacyclin-thromboxane ratio in sickle cell pregnant women, a situation that is also found in non-sickle pregnancies with PE and unexplained IUGR. Low dose aspirin (LDA) has been found to reduce the incidence of PE and IUGR in high-risk women due to its reduction of vasoconstrictor thromboxane whilst sparing prostacyclin, in effect "correcting" the ratio. It has been found to be safe for use in pregnancy and is recommended in obstetric guidelines for this use but has not been tested in sickle cell pregnancy. The investigators hypothesize that LDA would reduce the incidence of IUGR and PE in pregnant haemoglobin (Hb)SS women. The investigators also plan to build a machine-learning model to predict severe maternal outcomes in them. The investigators propose a multi-site, randomized, controlled, double blind trial comparing a daily dose of 100mg aspirin with placebo, from 12 - 28 weeks gestation until 36 weeks. The study sites are three teaching hospitals in Lagos and Ile-Ife, and twelve general hospitals and one federal medical centre within Lagos state, with the coordinating centre at the College of Medicine, University of Lagos (CMUL), Idi-Araba, Lagos. A total of 476 eligible pregnant HbSS and HbSC women will be recruited consecutively and randomly assigned to either group using a web-based app, sealed envelope. Each study group will comprise 238 pregnant women with SCD. All participants will be followed from recruitment till six weeks postpartum. They will have their body weight, blood pressure and haematocrit checked at each antenatal visit. Their full blood count, vital signs and oxygen saturation will be checked and recorded at each visit. Primary outcome measure will be birth weight below 10th centile for gestational age on INTERGROWTH 21 birthweight charts, and incidence of miscarriage or perinatal death. Analysis will be by intention to treat, and the main treatment effects will be quantified by relative risk with 95% confidence intervals, at a 5% significance level. The investigators plan to develop a prediction model to predict the risk of complications in these women using machine learning. The prediction outcome will be severe maternal outcomes comprising maternal near miss or death.

Conditions

Intrauterine Growth Restriction; Preeclampsia; Sickle Cell Disease; Pregnancy Complications

Keywords

Sickle cell disease; Low dose aspirin; Preeclampsia; Intrauterine growth restriction (IUGR); Pregnancy complications

Outcome Measures

Primary Outcomes (1)

• Number of babies with birth weight below 10th centile for gestational age on the WHO INTERGROWTH-21st birthweight charts, stillbirth or fetal death or miscarriages divided by the total number of babies delivered.

  Intrauterine growth restriction, perinatal death or miscarriage as a composite outcome.

  up to seven days after delivery.

Secondary Outcomes (13)

• Number of participants who will develop preeclampsia defined as hypertension and significant proteinuria after 20 weeks gestational age divided by the total number of participants.

  To be measured from date of randomization if greater than 20 weeks up till 6 weeks post-delivery if present

• Number of women that die at any gestational age during pregnancy or within 42 days after delivery from any cause arising from the pregnancy or its management but not from incidental or accidental causes, divided by the total number of participants.

  To be measured from randomization until date of death or 6 weeks post-delivery whichever comes first,

• Number of women delivered before 37 weeks gestational age divided by the total number of participants randomized.

  up to preterm delivery.

• Number of participants who will develop thromboembolism divided by the total number of participants.

  To be measured from randomization until date of death or 6 weeks post-delivery whichever comes first,

• Number of babies who died from 28 weeks gestational age up to seven days post delivery (comprising all still births and early neonatal deaths divided by total births reported as percentage.

  from 28 weeks gestational age till seven days post delivery

Study Arms (2)

Intervention

EXPERIMENTAL

Low dose aspirin (LDA) group will receive 100mg aspirin daily taken at once just before bedtime from 12 weeks gestational age or enrollment till 36 weeks gestational age.

Drug: Low-dose aspirin

Control

PLACEBO COMPARATOR

Placebo group will receive one tablet of the placebo which has same shape, size, thickness and colour as the LDA daily taken at once just before bedtime from 12 weeks gestational age or enrollment till 36 weeks gestational age.

Other: Placebo

Interventions

Low-dose aspirin DRUG

Low dose aspirin (LDA) group will receive 100mg aspirin daily taken at once just before bedtime from 12 weeks gestational age or enrollment till 36 weeks gestational age.

Also known as: Emprin

Intervention

Placebo OTHER

Placebo group will receive one tablet of the placebo which has same shape, size, thickness and colour as the LDA daily taken at once just before bedtime from 12 weeks gestational age or enrollment till 36 weeks gestational age.

Also known as: Emprin placebo

Control

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Eligibility is based on self-representation of gender identity and confirmed pregnancy.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years and above
• Singleton fetus
• Women whose genotypes are Haemoglobin SS or SC.
• weeks gestation or less at recruitment, estimated from the last menstrual period or by an early ultrasound scan.

You may not qualify if:

• Women with associated medical conditions in pregnancy e.g., HIV infection, diabetes mellitus, hypertension, renal disease, sickle nephropathy
• Multiple pregnancy
• Hypersensitivity to aspirin
• History of blood transfusion in the last 3 months
• Women who participated in the PIPSICKLE trial during their previous pregnancy.

Sponsors & Collaborators

• University of Lagos, Nigeria: lead

Study Sites (16)

Ajeromi General Hospital, Ajegunle, Lagos State

Ajegunle, Lagos, Nigeria

Location

Federal Medical Centre, Ebute Metta, Lagos State

Ebute-Metta, Lagos, Nigeria

Location

Lagos University Teaching Hospital

Idi Araba, Lagos, 100254, Nigeria

Location

Alimosho General Hospital, Igando, Lagos State

Igando, Lagos, Nigeria

Location

Lagos State University Teaching Hospital (LASUTH

Ikeja, Lagos, Nigeria

Location

General Hospital, Ikorodu, Lagos State

Ikorodu, Lagos, Nigeria

Location

General Hospital, Isolo, Lagos State

Isolo, Lagos, Nigeria

Location

General Hospital, Somolu, Lagos State

Somolu, Lagos, Nigeria

Location

Randle General Hospital, Surulere, Lagos State

Surulere, Lagos, Nigeria

Location

Obafemi Awolowo University Teaching Hospital OAUTH), Ife, Osun State

Ile-Ife, Osun State, Nigeria

Location

Lagos Island Maternity Hospital, Lagos

Lagos, 101001, Nigeria

Location

General Hospital, Gbagada, Lagos State

Lagos, Nigeria

Location

General Hospital, Ibeju-Lekki, Lagos State

Lagos, Nigeria

Location

General Hospital, Ifako Ijaiye, Lagos State

Lagos, Nigeria

Location

General Hospital, Orile-Agege, Lagos State

Lagos, Nigeria

Location

Mother and Child Centre, Amuwo-Odofin, Lagos

Lagos, Nigeria

Location

Related Publications (37)

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Related Links

• Published PIPSICKLE TRIAL protocol

MeSH Terms

Conditions

Fetal Growth Retardation; Pre-Eclampsia; Anemia, Sickle Cell; Pregnancy Complications

Interventions

Aspirin; Basigin

Condition Hierarchy (Ancestors)

Fetal Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypertension, Pregnancy-Induced; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins; Antigens, Neoplasm; Antigens; Biological Factors

Study Officials

• Bosede B Afolabi, DM (Nott)

  College of Medicine, University of Lagos

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind design. An unblinded pharmacist does the drug packaging and has the code for drug identification. All other members of the research team and patients are blinded and do not know what each drug is.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The clinical trial aspect is a multi-centre parallel, double blind, superiority randomized controlled trial, with women allocated in a 1:1 ratio. Participants are randomized into two groups. One group receiving low dose aspirin (LAD) 100mg daily from 12 weeks or from enrollment to 36 weeks gestational age. The second group receives a placebo tablet that looks exactly like the LAD in colour, size and shape also one tablet daily from 12 weeks or from enrollment to 36 weeks gestational age.

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: February 24, 2022
• Study Start: July 1, 2020
• Primary Completion: October 29, 2024
• Study Completion: November 21, 2024
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The IPD and supporting information will be made available at the time of first paper publication and will be made available for a period of 2 years
• Access Criteria: 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.

Locations

NG (16)