E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic hypertension in pregnancy |
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E.1.1.1 | Medical condition in easily understood language |
Long standing high blood pressure treatment in pregnancy |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036695 |
E.1.2 | Term | Primary hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039834 |
E.1.2 | Term | Secondary hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015488 |
E.1.2 | Term | Essential hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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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 |
To undertake a feasibility study for a randomised controlled trial comparing labetalol and nifedipine in pregnant women with chronic hypertension, with planned assessment of ethnic variation in drug response
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E.2.2 | Secondary objectives of the trial |
•To evaluate maternal and perinatal outcomes
•To determine health resource use
•To assess whether differential response to antihypertensive treatments is explained by biomarkers and/or vascular function parameters
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Chronic hypertension (defined as diastolic blood pressure (BP) >=90mmHg present at booking or before 20 weeks' gestation, or requiring treatment outside pregnancy and/or at time of referral)
•Gestation 12-28 weeks’ gestation
•Singleton pregnancy
•Able to provide informed consent
•Age >=18 years
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E.4 | Principal exclusion criteria |
•Contraindication to labetalol (including asthma, uncontrolled heart failure, Prinzmetal's angina, marked bradycardia, hypotension, sick sinus syndrome, second- or third- degree AV block, cardiogenic shock, metabolic acidosis, severe peripheral arterial disease; phaeochromocytoma) or nifedipine (including cardiogenic shock; advanced aortic stenosis; within 1 month of myocardial infarction; unstable or acute attacks of angina)
•Insufficient understanding of the trial
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Process Endpoint:
•Number recruited per site per month
Primary Clinical Endpoint:
•Highest systolic BP post-randomisation
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Women will take part in the trial for a maximum of 30 weeks of their pregnancy. We plan to recruit 114 women and anticipate the last woman will be recruited one year after commencing the study, so the study would end 30 weeks after this time. Evaluation of both primary outcomes would be possible at this point. |
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E.5.2 | Secondary end point(s) |
Clinical:
•Maternal outcomes including:
-maternal morbidity or mortality (pre-eclampsia, eclampsia, intracranial haemorrhage or infarct, myocardial ischaemia/infarction, intubation, pulmonary oedema, hepatic dysfunction, acute renal insufficiency, placental abruption, post-partum haemorrhage)
- gestation at delivery
- mode of delivery
- indication for delivery
- number of episodes of systolic BP >=160mmHg, >=150mmHg (including home monitoring)
- diastolic BP <80mmHg
- need for additional oral or parenteral antihypertensives
•Perinatal outcomes including:
-neonatal morbidity (admission to neonatal unit (length and place of stay), respiratory distress syndrome, need for ventilator support, intraventricular haemorrhage, confirmed infection, necrotising enterocolitis, seizures, encephalopathy, retinopathy of prematurity, other indications and main diagnoses related to neonatal unit admission)
- abnormal umbilical artery Doppler waveforms,
- stillbirth
- neonatal death
- birth weight
- birth weight centile
- umbilical artery pH at birth
•Health resource use outcomes including:
- number of antenatal attendances (clinic and day unit)
- maternal admission nights (ward, delivery suite, intensive care)
- neonatal admission nights (including level of care)
•Explanatory biomarker and vascular function assessments
Process:
•Medication adherence (through self-report and pill count)
•Side-effects of medication
•Satisfaction with medication (assessed through postnatal questionnaire) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Most of the secondary outcomes will be evaluated immediately once the last recruit has been followed up at 6 weeks post delivery of the last participant, but the explanatory biomarker studies may take up to 3 years to complete. |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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
| 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 | 3 |
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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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 |