Mechanisms of Refractory Hypertension (Carvedilol)

NCT ID: NCT02357004

Last Updated: 2020-06-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2020-01-31

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.

Conditions

Hypertensive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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).

Group Type: EXPERIMENTAL

Carvedilol

Intervention Type: DRUG

CR 40 mg daily in addition to normal BP medications

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).

Group Type: EXPERIMENTAL

Chlorthalidone

Intervention Type: DRUG

12.5 mg daily in addition to normal BP medications

Interventions

Carvedilol

CR 40 mg daily in addition to normal BP medications

Intervention Type: DRUG

Chlorthalidone

12.5 mg daily in addition to normal BP medications

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

David Calhoun

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David A. Calhoun, MD

Role: PRINCIPAL_INVESTIGATOR

Cardiology Department - University of Alabama at Birmingham

Other Identifiers

A000502641

Identifier Type: -

Identifier Source: org_study_id