Mechanisms of Refractory Hypertension (Carvedilol)

Not Applicable

Withdrawn

• Conditions: Hypertensive
• Interventions: Drug: Carvedilol; Drug: Chlorthalidone

• Registration Number: NCT02357004
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

The purpose of this protocol is test whether patients with hypertension refractory to antihypertensive treatment have evidence of excessive sympathetic (i.e., nervous system) activity.

Detailed Description

Refractory hypertension refers to high blood pressure that is failing conventional antihypertensive therapies. In a retrospective assessment of such patients in our clinic we observed that resting clinic heart rates were higher in patients with refractory hypertension compared to patients with controlled hypertension. This observation has led to the hypothesis that refractory hypertension is caused by excessive sympathetic output. This protocol is designed to test this hypothesis by comparing the BP response to carvedilol verses chlorthalidone in patients with refractory hypertension. If their extreme treatment resistance is neurogenic is etiology, a significantly larger BP response to carvedilol should occur compared to chlorthalidone.

Study Timeline

• Study First Submitted: 2015-01-22
• Study Start: 2015-02
• Study First Submitted QC: 2015-02-02
• Study First Posted: 2015-02-06
• Primary Completion: 2020-01-31
• Study Completion: 2020-01-31
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-10
• Last Update Posted: 2020-06-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Uncontrolled clinic BP (>140/90 mmHg)
• Receiving 5 or more antihypertensive agents including an ACE inhibitor or ARB, calcium channel blocker, and chlorthalidone 25 mg

Exclusion Criteria

• Current use of an alpha or beta or combined alpha-beta antagonist
• Known allergy to alpha-beta antagonists
• CKD (eGFR <40 ml/min/m2)
• MI, stroke or episode of CHF exacerbation within 3 months
• Bradycardia <50 bpm; history of 2nd or 3rd degree heart block unless treated by a pacemaker
• Pregnant or breast-feeding women
• Known hypersensitivity to chlorthalidone or other sulfonamide-derived drugs

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carvedilol	Carvedilol	Carvedilol CR 40 mg daily in addition to their normal BP medications. Subjects will be seen in follow-up at 2-week intervals for the duration of the 8-week intervention period. If the clinic BP remains elevated (\>140/90 mmHg) at any of the follow-up visits, the study medication will be titrated up to carvedilol CR 80 mg daily (subjects will take 2 of the study pills).
Chlorthalidone	Chlorthalidone	Chlorthalidone 12.5 mg daily in addition to their normal BP medications. Subjects will be seen in follow-up at 2-week intervals for the duration of the 8-week intervention period. If the clinic BP remains elevated (\>140/90 mmHg) at any of the follow-up visits, the study medication will be titrated up to chlorthalidone 25 mg daily (subjects will take 2 of the study pills).

Primary Outcome Measures

Name	Time	Method
% of subjects who achieve BP control (<140/90 mm Hg)	8 weeks after baseline	BP will be measured 8 weeks after starting carvedilol and after starting chlorthaidone. The percent of subjects with BP of \<140/90 mm HG in each group will be reported.