E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Delivery of a baby between 24+0 and 36+6 weeks gestation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10032405 |
E.1.2 | Term | Other preterm infants |
E.1.2 | System Organ Class | 100000004868 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is testing whether women between 28+0 and 35+6 weeks pregnant who come to hospital with signs and/or symptoms of preterm labour would be willing to take a medication (pravastatin) or placebo in a blinded fashion for 7 days. |
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E.2.2 | Secondary objectives of the trial |
1) To see if pravastatin when compared to placebo is associated with a longer time to delivery, fewer contractions, and lower markers of inflammation in both the mother and fetus in women with preterm labour. 2) To see if pravastatin when compared to placebo improves outcomes for both mother and baby. 3) To monitor the average time from when a participant is first established as eligible for the trial to when they get the first dose of study drug. 4) To establish how acceptable the study is to participants after completing the protocol. 5) To measure compliance with treatment. 6) To establish whether the blood concentrations of study drug in this population are the same as currently published data. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Gestation between 28+0 and 35+6 weeks inclusive (based on dating scan obtained at ≤ 16 weeks gestation) • Singleton pregnancy • Aged 16 years or above • Not previously recruited to this study in this pregnancy • Intact membranes • A positive fetal fibronectin test OR a short cervical length ( 15mm) on ultrasound examination OR cervical dilation ≥ 3cm and less than fully dilated • Uterine activity defined as ≥ 1 palpable contraction over 20 minutes of CTG monitoring. • No major congenital anomalies evident on the 20 week anomaly scan, or any further anomaly scans performed subsequently. If an anomaly is present, this should be classified as per ICD-10 codes and minor anomalies discussed for inclusion on a case by case approach involving the clinical team, the PI and the participant. • Not demonstrating any of the exclusion criteria
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E.4 | Principal exclusion criteria |
• • Immediate delivery deemed necessary for fetal or maternal reasons as determined by a senior clinician. • Pre-labour, preterm rupture of membranes in the index pregnancy • Obstetric Cholestasis as defined by RCOG (RCOG Green-Top Guideline, Number 43) • Established severe pre-eclampsia or HELLP syndrome as defined by NICE guidance (Hypertension in pregnancy: diagnosis and management | Guidance and guidelines | NICE n.d.) • Known History of hepatic or renal impairment • Ingestion of drugs thought to alter the pharmacokinetics or efficacy of statins, including erythromycin and/or nifedipine. • Taking any one of the prohibited drugs as listed the SmPC and in 5.7.3 • Lactose intolerance (due to excipient in Pravastatin and placebo) • Current or previous alcohol misuse • Personal or first degree relative with heritable muscle disorders • Participating in another CTIMP trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Recruitment, retention and outcome collection of 40 Participants in established preterm labour. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Recruitment of participant number 40 |
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E.5.2 | Secondary end point(s) |
1) Retention, adherence and ability to collect clinical outcomes from participants 2) Time to delivery from presentation and gestation at delivery 3) Contraction frequency from presentation to delivery or cessation of regular uterine activity. 4) Maternal markers of inflammation including, but not limited to: IL-6, IL-10, IL-13, IL-17, TNFa, IL-1RA, sTNF-RI,sTNF-R2, and HO-1, as well as levels of the soluble IL-6R and the inhibitor spg130 (abbreviated hereafter to ‘Inflammatory Profile’) 5) Fetal measures of inflammation (cord IL-1, IL-6, IL-8) as well as levels of sIL-6R and sgp130. 6) Adverse events (maternal and fetal) 7) Time from ‘time first seen’ to delivery of first dose of trial medication 8) Compliance with 7 days of blinded treatment 9) Acceptability of the trial to those who have participated 10) Pharmacokinetic parameters as compared with current published data 11) Maternal outcomes: a. Proven maternal infection b. Safety of intervention to mother (self-reported AEs and biochemical monitoring of liver function tests and creatinine kinase). c. Pre-labour ROM d. Duration, location and level of care of hospital stay following presentation with suspected preterm labour AND following delivery. 12) Neonatal outcomes: a. Neonatal morbidity (a composite measure of neonatal outcomes, including neurological, respiratory, gastrointestinal and cardiological measures, gestation and weight at birth, place and length of stay following delivery, evidence of sepsis and feeding type.) b. Neonatal mortality c. Safety of intervention |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At estimated date of delivery + 28 days for the last participant recruited |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS (Expected data of delivery plus 28 days) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |