Monotherapy Versus Dual Therapy for Initial Treatment for Hypertension

• Status: Unknown status
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

To test whether the current custom of initiating treatment for hypertension with a single drug is less effective in the short-term than initial combination therapy, and results in the eventual need for comparatively more antihypertensive drug therapy.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Cambridge
• Collaborator: British Heart Foundation
• Treatments: Hydrochlorothiazide; Losartan

Criteria

Patients must meet ALL inclusion criteria

1. Aged 18-79

2. Male subjects or female subjects taking adequate contraception such as the oral contraceptive pill, an intra uterine device or who are surgically sterilised or postmenopausal Females

3. BP ≥150 mmHg (systolic) OR ≥ 95 mmHg (diastolic). Patients may be included if the PI anticipates BP criteria for inclusion will be met at randomisation

4. Either never-treated or received a maximum of one antihypertensive drug class in the previous year

Patients will be excluded for ANY ONE of the following reasons

1. Clinic SBP > 200 mmHg or DBP > 120 mmHg, with PI discretion to override if home BP measurements are lower

2. Secondary or accelerated phase hypertension

3. eGFR < 45 mls/min

4. Contra-indication or previous intolerance to any trial therapy

5. Failure to record required home BP readings during placebo run-in.

6. Significant co-morbidity (investigator opinion but to include alcoholism, terminal illness, documented non-attendance at clinics etc)

7. Diabetes type 1

8. Plasma K+ outside normal range on two successive measurements during screening

9. Requirement for treatment with ≥2 drugs (which can be a CCB and/or {ACEi OR ARB OR direct renin inhibitor OR β-blocker}) in order to reduce blood pressure to ≤180/120 mmHg

10. Requirement for diuretic therapy (other than for hypertension)

11. Requirement for ACE inhibitor (or ARB) therapy (other than for hypertension)

12. Absolute contra-indications to any of the study drugs (listed on their data-sheet)

13. Current therapy for cancer

14. Anticipation of change in medical status during course of trial (e.g. planned surgical intervention requiring >2 weeks convalescence , actual or planned pregnancy)

15. Inability to give informed consent

16. Participation in a clinical study involving an investigational drug or device within 4 weeks of screening.

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 the subject's lifespan or ability to complete the study (eg, alcohol or drug abuse, disabling or terminal illness, mental disorders).

18. Treatment with any of the following prohibited medications:

1. Oral corticosteroids within 3 months of screening. Treatment with systemic corticosteroids is also prohibited during study participation.

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.

2. 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.

3. 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.

4. The use of sympathomimetic decongestants is permitted; however, not within 1 day prior to any clinic visit/BP assessment.

5. The use of theophylline is permitted; however, the dose must be stable for at least 4 weeks prior to screening and throughout study participation.

6. The use of phosphodiesterase (PDE) type V inhibitors is permitted; however, subjects must refrain from taking these medications within 1 day of screening or any subsequent study visit.

7. The use of alpha-blockers is not permitted - with the exception of afluzosin and tamsulosin for prostatic symptoms