Mechanisms of Refractory Hypertension (Carvedilol)

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02357004

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertensive	Drug: Carvedilol Drug: Chlorthalidone	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Study Start Date :

Feb 1, 2015

Actual Primary Completion Date :

Jan 31, 2020

Anticipated Study Completion Date :

Jan 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Drug: Carvedilol CR 40 mg daily in addition to normal BP medications
Experimental: 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).	Drug: Chlorthalidone 12.5 mg daily in addition to normal BP medications

Arm

Intervention/Treatment

Experimental: 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).

Drug: Carvedilol

CR 40 mg daily in addition to normal BP medications

Experimental: 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).

Drug: Chlorthalidone

12.5 mg daily in addition to normal BP medications

Outcome Measures

Primary Outcome Measures

% 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

Principal Investigator: David A. Calhoun, MD, Cardiology Department - University of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

David Calhoun, Principal Investigator, University of Alabama at Birmingham

ClinicalTrials.gov Identifier:

NCT02357004

Other Study ID Numbers:

A000502641

First Posted:

Feb 6, 2015

Last Update Posted:

Jun 12, 2020

Last Verified:

Jun 1, 2020

Additional relevant MeSH terms:

Carvedilol

Chlorthalidone

Study Results

No Results Posted as of Jun 12, 2020