Prospects for the Prevention of Pregnancy-induced Hypertension and Preeclampsia Trial (4P)

Prospects for the Prevention of Pregnancy-induced Hypertension and Preeclampsia (4P) - a Randomised, Placebo-controlled, Double-blind Clinical Trial

Hypertensive disorders of pregnancy (HDP) are with 50.000 deaths every year one of the major causes of maternal mortality worldwide, especially in low and middle income countries. This trial aims to determine whether a daily dose of combined low-dose aspirin, calcium, vitamin D3, folic acid and vitamin B12 in pregnancy reduces the incidence of pregnancy-induced hypertension in women at risk. Secondary and tertiary objectives include other maternal and neonatal outcomes.

Study Overview

• Status: Unknown
• Conditions: Pregnancy Induced Hypertension
• Intervention / Treatment: Drug: Combined aspirin and multinutrient supplement; Other: Daily text reminder text messages

• Study Type: Interventional
• Enrollment (Anticipated): 440
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Joyce L Browne, MD, MSc; Phone Number: +31649650071; Email: J.L.Browne@umcutrecht.nl
• Study Contact Backup: Name: Diederick E Grobbee, MD, PhD; Phone Number: +31 (0)88 755 9358; Email: D.E.Grobbee@umcutrecht.nl

Study Locations

• Ghana
  • Accra, Ghana
    • LA General Hospital
    • Contact: Patrick Frimpong, MBChB; Phone Number: +233244270320; Email: patrickfrimpong@hotmail.com
    • Principal Investigator: Patrick Frimpong, MBChB
  • Accra, Ghana
    • Ridge Regional Hospital
    • Contact: Emmanuel K Srofenyoh, MBChB; Phone Number: +233208118509; Email: emmanuelsrofenyoh@gmail.com
    • Principal Investigator: Emmanuel K Srofenyoh, MBChB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• <16 weeks of gestation and over 18 years of age,
• Intention to have subsequent antenatal visits and delivery at the same clinic.
• Can receive text messages by phone or through the phone of a proxy.
• A moderate to high risk (>20%) of developing PIH

Exclusion Criteria:

• Pre-existing hypertension or hypertension before 20 weeks gestation.
• Likely non-compliance with the protocol in view of the treating physician
• Comorbidity interfering with the protocol
• Known contraindications to Investigational Product components

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Combined aspirin and multinutrient supplement; In a single capsule, the following will be combined: 80mg low-dose aspirin, 1.2 grams calcium, 600 IU vitamin D, 5mg folic acid and 1000 ug vitamin B12	Drug: Combined aspirin and multinutrient supplement; Single capsule with 80mg low-dose aspirin, 1.2 grams calcium, 600 IU vitamin D, 5mg folic acid and 1000 ug vitamin B12 mixed.; Other: Daily text reminder text messages
PLACEBO_COMPARATOR: Placebo; 5mg folic acid, cellulose filler	Other: Daily text reminder text messages

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of pregnancy-induced hypertension (PIH) in pregnancy	Development of a de novo systolic blood pressure (SBP) of > 140 mmHg, diastolic blood pressure (DBP) of >90 mmHg, measured at least twice.	up to 2 days after delivery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal/obstetric outcomes	maternal death, preeclampsia, eclampsia, hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, hemorrhage, caesarian section, other complications during pregnancy or delivery	6-16 weeks gestation, 16-24 weeks gestation, 26-36 weeks gestation, delivery and first days after
Neonatal and infant outcomes	preterm birth, Intra uterine death, stillbirth, neonatal mortality, congenital abnormality, Neonatal Intensive Care Unit (NICU) admission or pediatrician referral, birth weight, small for gestational age, apgar scores, other adverse effects. Infant outcomes: weight and height, health, occurrence of disease and general health status	6-16 weeks gestation, 16-24 weeks gestation, 26-36 weeks gestation, delivery and first days after
Number of participants with (severe) adverse events as a measure of safety and tolerability	Number of patients with (severe) adverse events. Adverse events include any undesirable experience associated with the use of a medical product. Related to the product, bleeding incidences (including bruises), nausea, vomiting, will be explicitly reported. Severe adverse events are: death, life-threatening conditions, (prolonged) hospitalization, disability and permanent damage to mother or fetus, congenital abnormality, or other important (serious) medical events.	1 year

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: University of Ghana; Ghana Health Services
• Investigators: Principal Investigator: Diederick E Grobbee, MD PhD, UMC Utrecht; Principal Investigator: Patrick Frimpong, MBbCh, Ghana Health Services; Principal Investigator: Emmanuel K Srofenyoh, MBbCb, Ghana Health Services

Study record dates

Study Major Dates

• Study Start: January 1, 2018
• Primary Completion (ANTICIPATED): April 1, 2018
• Study Completion (ANTICIPATED): August 1, 2018

Study Registration Dates

• First Submitted: November 26, 2013
• First Submitted That Met QC Criteria: December 10, 2013
• First Posted (ESTIMATE): December 11, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): November 25, 2016
• Last Update Submitted That Met QC Criteria: November 23, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: pre-eclampsia; preeclampsia; pregnancy induced hypertension; gestational hypertension; hypertensive disorders in pregnancy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: GHS-ERC: 05/05/2012