E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obstetric cholestasis (OC) is a serious problem in pregnancy. It affects about 1 in 150 pregnancies, about 4500 women per year in the UK. Affected women develop severe itching and sometimes jaundice. More importantly, the condition is associated with increased risks to the unborn baby, premature delivery, and is believed to be an important cause of stillbirth. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049055 |
E.1.2 | Term | Cholestasis of pregnancy |
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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 |
The main objective is to collect data to finalise the design of a factorial trial for the main to test the hypotheses that the use of a ursodeoxycholic acid reduces itching, pre-term delivery and fetal morbidity and that active management by planned delivery at 37-38 weeks reduces fetal morbidity. In the present project we wish to collect data to finalise the design of such a trial specifically to:
. Measure recruitment to the two factorial interventions separately |
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E.2.2 | Secondary objectives of the trial |
Secondary objecties are:
1. Relate recruitment rates to disease severity 2. Estimate a realistic recruitment rate for the definitive trial 3. Measure acceptability of randomisation among potential participants offered trial entry 4. Measure compliance with each treatment arm 5. Measure the completeness of outcome data 6. Finalise the design including the sample size calculation for the definitive trial 7. Measure medium term (6 weeks) maternal and fetal outcomes for the definitive trial.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
1. 24+0 to 37+6weeks pregnant; (24+0 – 40+6 weeks) UDCA arm only 2. age 18-55 years 3. Diagnosed as OC based on history of pruritus in pregnancy and deranged biochemical parameter (random bile acid >14 µmoles/litre or raised ALT over 100 U/L) 4. Clinician responsible for care is uncertain whether UDCA or early delivery is beneficial 5. Patients who otherwise fulfil the recruitment criteria, but incidentally have either hepatitis C, or cholelithiasis, or both, are eligible and may be included. 6. Women with multiple pregnancies who are otherwise eligible may be included in the UDCA/placebo comparison only. 7. Willing to participate in the trial and able to give informed consent.
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E.4 | Principal exclusion criteria |
Exclusion criteria
1. Dermatological and allergic causes for pruritus 2. Other causes of pruritus and deranged liver enzymes (except hepatitis C and cholelithiasis see above). 3. Hepatitis A, hepatitis B, pre-eclampsia, primary hepatic disorders, alpha-1 antitrypsin deficiency and current medications causing deranged liver enzymes. 4. Women unable or unwilling to consent 5. Known lethal fetal anomalies.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints:
• To measure total recruitment rate per 1000 deliveries/ annum • To measure total recruitment rate per eligible women
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
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 | Information not present in EudraCT |
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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No formal stopping rules applicable. Both treatments ie ursodeoxycholic acid and early delivery are commonly practiced for management of obstetric cholestasis. All adverse events will be reported to the DMEC. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |