Hypertension MedDRA version: 15.0 Level: PT Classification code 10020772 Term: Hypertension System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Trade Name: Spironolactone
Product Name: spironolactone
Pharmaceutical Form: Capsule
INN or Proposed INN: spironolactone
CAS Number: 52-
Sponsors
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Cambridge Clinical Trials Unit
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria: • Patients aged 18-79 years; • Patients will all have hypertension that is not controlled to target: clinic systolic BP = 5 mmHg above target (i.e. = 140 mmHg for non-diabetic hypertensives or = 135 mmHg for diabetics), under one of the following conditions: a) Treatment for at least 3 months with lisinopril 20 mg (A) + amlodipine 10 mg (C)+bendroflumethiazide 2.5 mg (D) or their equivalents‡ b) Patients who have received the three drugs or equivalents specified in a), and are either intolerant to one category, or tolerate only a lower dose (e.g. amlodipine 5 mg or lisinopril 10 mg) c) Patients receiving the three drugs or equivalents specified in a), who are receiving additional drugs for their hypertension, may be included if the investigator 1) feels it is appropriate to stop these additional drugs at the screening visit and 2) anticipates that the BP criteria for inclusion will be met when re-checked at the baseline visit Patients may be included if the PI anticipates BP criteria for inclusion will be met at randomisation. 3. Patients with a home systolic BP average of >130 mmHg or within 15mmHg of clinic BP over the 4 days prior to the baseline visit. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Inability to give informed consent; 2. Participation in a clinical study involving an investigational drug or device within 4 weeks of screening; 3. Secondary or accelerated hypertension; 4. Type 1 diabetes; 5. eGFR2 weeks convalescence); 9. Absolute contra-indication to study drugs (e.g. asthma) or previous intolerance of trial therapy; 10. Sustained atrial fibrillation; 11. Recent (200 mmHg or diastolic BP >120mmHg, with PI discretion to override if home BP measurements are lower 17. 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 that patients life-span or ability to complete the study (e.g. alcohol or drug abuse, disabling or terminal illness, mental disorders); 18. Treatment with any of the following medications; a. Oral corticosteroids within 3 months of screening. Treatment with systemic corticosteroids is also prohibited during study participation; b. Chronic stable use, or unstable use of NSAIDs (other than low dose aspirin) is prohibited. Chronic use is defined as >3 consecutive or non-consecutive days of treatment per week. In addition intermittent use of NSAIDs is strongly discouraged throughout the study and NSAIDs if required, must not be used for more than a total of 2 days. For those requiring analgesics during the study, paracetamol is recommended. c. The use of short acting nitrates (e.g. sublingual nitroglycerin) is permitted. However, participants should not take P2 Protocol v7.1 26 May 11 Page 14 of 69 short acting oral nitrates within 4 hours of screening or an subsequent visit; d. The use of long acting nitrates (e.g. Isordil) is permitted but the dose must be stable for at least 2 weeks prior to screening and randomisation; e. The use of sympathomimetic decongestants is permitted , however, not within 1 day prior to any study visit/BP assessment; f. The use of theophylline is permitted but the dose must be stable for at least 4 weeks prior to screening and throughout the study; g. The use of phosphodiesterase type V inhibitors is permitted; however study participants must refrain from taking these medications for at least 1 day prior to screening or any subsequent study visits;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary outcome will be the difference in home BP between the best drug predicted by the patient’s plasma renin and the observed best drug. (High-renin, i.e. highest tertile, predicts beta-blocker (bisoprolol) best; low-renin, i.e. lowest tertile, predicts further-diuretic (spironolactone) best; normal-renin (i.e. middle tertile) predicts alpha-blocker (doxazosin) best.;Main Objective: The primary objective is to test our primary hypothesis which states that the commonest cause of resistant hypertension is excessive sodium retention, and that further diuretic therapy, i.e. spironolactone will be superior to other potential "add-on drugs" for people with inadequate blood pressure control despite treatment with three drugs, i.e. Ace Inhibitors, Calcium Channel Blockers and Diuretics (A+C+D).; Primary end point(s): The Primary Outcome Measure will be the difference in home systolic BP averages between each active drug and placebo, at the end of the 12 week treatment cycle, when each drug is taken at maximum tolerated dose. ;Timepoint(s) of evaluation of this end point: End of 12 week treatment cycle | — |
Countries
United Kingdom
Outcome results
None listed