Hypertension MedDRA version: 9.1 Level: LLT Classification code 10020772 Term: Hypertension
Conditions
Interventions
Trade Name: Amiloride
Product Name: Amiloride
Pharmaceutical Form: Capsule*
Trade Name: Hydrochlorothiazide
Product Name: Hydrochlorothiazide
Pharmaceutical Form: Capsule*
Sponsors
Cambridge University Hospitals NHS Foundation Trust and University of
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each of the following conditions must be satisfied. Patients can proceed to placebo run-in if biochemical data is available from previous 6 months, but cannot proceed to randomised treatment if eligibility not confirmed by baseline sample: 1. Age 18-79 2. Diagnosis of hypertension according to BHS criteria 3. Clinic seated SBP (mean of 2nd & 3rd readings after 10 minutes rest) on permitted background treatment >= 145 mmHg 4. Indication for diuretic treatment: (a) Untreated + (age>55 AND/OR Black AND/OR renin 94cm male (>90 if Asian), > 80 female + two of: - SBP = 130 or DBP = 85 mmHg - Fasting glucose >5.6mmol/l - Fasting Triglycerides > 1.7 mmol/l (or on rx) - HDL =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusions : The presence of any of the following will preclude patient inclusion • Diabetes (types 1 or 2) • Secondary hypertension • eGFR 170 mmHg • Home DBP at the end of placebo run-in >115 mmHg • Requirement for treatment with >2 drugs (which can be a CCB and/or {ACEi OR ARB OR ß-blocker}) in order to reduced blood pressure to =170/115 mmHg • Requirement for diuretic therapy (other than for hypertension) • Requirement for both ß-blockade and ACE inhibitor (or ARB) therapy • Absolute contra-indications to any of the study drugs (listed on their data-sheet) • Current therapy for cancer • Anticipation of change in medical status during course of trial (e.g. surgical intervention requiring G.A., actual or planned pregnancy) • Inability to give informed consent • Not on stable doses of all concomitant medications for a minimum of 4 weeks prior to randomisation • Participation in a clinical study involving an investigational drug or device within 4 weeks of screening. • Any concomitant condition that, in the opinion of the investigator, may adversely affect the safety and/or efficacy of the study drug or severely limit the subject’s lifespan or ability to complete the study (eg, alcohol or drug abuse, disabling or terminal illness, mental disorders). • Treatment with any of the following prohibited medications: a. Oral corticosteroids within 3 months of Screening. Treatment with corticosteroids is also prohibited during study participation. b. Acetylsalicylic acid in excess of 325 mg per day. c. Chronic stable or unstable use of non-steroidal anti-inflammatory drugs (NSAIDs) other than acetylsalicylic acid is prohibited. Chronic use is defined as >3 consecutive or nonconsecutive days of treatment per week. In addition, the intermittent use of NSAIDs is strongly discouraged throughout the duration of this study. If intermittent treatment is required, NSAIDs must not be used for more than a total of 2 days. For all subjects requiring analgesic or anti-pyretic agents, the use of paracetamol is recommended during study participation. d. The use of short-acting oral nitrates (eg, sublingual nitroglycerin) is permitted; however, subjects should not take short-acting oral nitrates within 4 hours of Screening or any subsequent study visit. e. The use of long-acting oral nitrates (eg, Isordil) is permitted; however, the dose must be stable for at least 2 weeks prior to Screening and Randomisation. f. The use of sympathomimetic decongestants or ß-agonists is permitted; however, not within 1 week prior to Screening or Randomisation. In addition, use of these medications will be prohibited within 1 day prior to any clinic visit. g. The use of theophylline is permitted; however, the dose must be stable for at least 4 weeks prior to Screening and throughout study participation. h. The use of phosphodiesterase (PDE) type V inhibitors is permitted; however, subjects must refrain from taking these medications within 3 days of Screening or any subsequent study visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether a K+-sparing diuretic improves glucose tolerance in patients with hypertension and at least one other component of the metabolic syndrome.;Secondary Objective: To demonstrate improved efficacy and tolerability of combining diuretics, compared to taking one class alone.;Primary end point(s): 1.A change in blood glucose levels between 0-6 months. This will be measured two hours after oral ingestion of a 75 G glucose drink, following overnight fasting. This will be performed on the final day of dosing of the placebo run-in and end of blinded treatment 2.Change in systolic BP from end of placebo run-in after six months. For calculation of this change we will use the mean of duplicate readings, taken as close as convenient for each subject to 8.0 and 8.0 pm on the last three days of: •placebo run-in, and •the end of blinded treatment (6 months). | — |
Countries
United Kingdom
Outcome results
None listed