A Proof of Principle, Double-Blind, Randomised Placebo-Controlled,Multi-centre Trial of pravaStatin to Ameliorate Early Onset Pre-eclampsia - StAmP

Phase 1

Conditions: Pre-eclampsia
Level: LLTClassification code 10036485Term: Pre-eclampsia
Level: LLTClassification code 10040444Term: Severe pre-eclampsia

Registration Number: EUCTR2010-023502-12-GB

Lead Sponsor: niversity College London

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: Female

Target Recruitment: Not specified

Inclusion Criteria

In order to be randomised into the StAmP trial, all eligibility criteria must be satisfied. There are no maternal age restrictions for participation, however mothers should be considered to have Gillick competence” to be capable of providing informed consent. Investigators will be asked to confirm each eligibility criteria at randomisation. Inclusion Criteria: To be eligible for the StAmP Trial, the women must: 1. Be between 24+0 weeks’ and 31+6 weeks’ gestation 2. Have a singleton pregnancy 3. Have a diagnosis of early onset Pre-eclampsia (according to definition below) 4. Be considered capable of safely continuing the pregnancy for 48 hours or more, as determined by the attending clinician 5. Obstetrician and neonatologist believe the fetus is likely to be viable 6. No major anomalies evident on the 20-week anomaly scan. Any anomaly should be assessed by the Principal Investigator and discussed with the Chief Investigator, following classification of the anomaly according to the ICD10 codes. All major anomalies will be excluded, but minor anomalies, subject to agreement between the PI and CI will be included 7. Be capable of understanding the information provided, with use of an interpreter if required 8. Give written informed consent Definition of Pre-eclampsia (24-31+6 weeks gestation) The minimum clinical criteria required to establish a diagnosis of pre-eclampsia are the first two criteria below. The third criterion is relevant if there is chronic hypertension, preceding pregnancy. The other criteria (4-6) are often present in early pre-eclampsia, but are not essential for diagnosis for pre-eclampsia. 1. New onset hypertension after 20 weeks gestation defined as diastolic BP greater than 90 mmHg, using Korotkoff sound 5 to define the diastolic level. 2. New onset proteinuria 2+ or more on standard urinary dipstick tests confirmed by proteinuria PCR ratio of greater than 30mg/mmol on spot urine test or >300mg/24 hours on a 24 hour urine collection. 3. Women who have chronic hypertension, the appearance of new onset proteinuria, (defined above), a sudden increase of blood pressure, thrombocytopenia (platelets <100), elevated transaminases, or a sudden increase in proteinuria in those who have pre-existing proteinuria. 4. Liver transaminases may be increased 5. Serum creatinine (SCr) may be increased 6. Platelet count may be decreased
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Any women, who at the point of randomisation, exhibit any of the following are not eligible for the trial: 1. Eclampsia 2. Current use of statins 3. Contraindications to statin use (other than pregnancy) including: - Hypersensitivity to pravastatin or any of its excipients - Active liver disease or elevation of serum transaminases not thought to be related to pre-eclampsia - Pre-pregnant renal insufficiency (creatine clearance <30ml/min) - Concomitant administration of potent CYP3A4 inhibitors 4. Imminent transfer to a non-trial centre due to unavailability of neonatal cots. 5. Participation in any other blinded, placebo-controlled trials of investigational medicinal products in pregnancy. 6. Significant uncertainty regarding gestational age. Under 24 weeks' gestation, pregnancies are often not considered viable and therefore women with pre-eclampsia less than 24 weeks gestation will be excluded. Women with pre-eclampsia around 32 weeks’ gestation are often delivered when the mother is stable and therefore we will exclude women who develop pre-eclampsia over 32 weeks’ gestation. For this reason, if there is any uncertainty about the gestational age, the mother should not be approached for randomisation. 7. Women to be treated as an outpatient will be excluded.