Treatment of Hypertension In Adults With ThiaZIDES: Pragmatic Trial Pilot Study

NCT ID: NCT02591628

Last Updated: 2017-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2027 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2017-07-31

Brief Summary

This proposed pilot study will test methods and feasibility for a large pragmatic clinical trial comparing two inexpensive, first-line drugs for treating high blood pressure to determine if one is superior in preventing serious cardiovascular events and death. It will develop and test novel approaches to conducting trials that will be faster, less expensive, and more realistic by being embedded in a typical practice setting and using advanced health information technology.

Detailed Description

For several decades, U.S. hypertension treatment guidelines have recommended a low-dose diuretic such as hydrochlorothiazide (HCTZ) or chlorthalidone (CTD) as initial monotherapy in a stepped-care approach or as part of an initial two-drug combination. In numerous large clinical trials, CTD-based regimens have significantly reduced rates of cardiovascular events such as stroke, heart failure, and cardiovascular mortality compared with placebo, usual care, or active comparators. In contrast, few outcome studies have compared HCTZ-based regimens with other treatments, and they have generally found HCTZ to be less effective than non-thiazide comparators in preventing cardiovascular events. The two drugs have never been compared directly in a large trial. Despite the empirical evidence favoring CTD, HCTZ is much more widely used in clinical practice. The proposed R34 is a pilot study conducted in two large integrated health systems to test methods and feasibility for an eventual pragmatic randomized trial comparing the effectiveness of HCTZ and CTD for preventing cardiovascular events and mortality. Using a cluster-randomized design, investigators will allocate 40 primary care physicians and their adult hypertensive patients who currently use HCTZ (N=2,000) to either convert HCTZ users to CTD (intervention group) or to continue HCTZ (usual care group). The pilot study and planned full-scale trial will use existing health care infrastructure and electronic health records to identify eligible study subjects, distribute study medication, and collect operational and outcomes data. For this pilot study, Aim 1 will document that the intervention is delivered as intended. Aim 2 will compare safety in intervention and usual care patients. Aim 3 will refine the pilot study design and identify critical factors for intervention success using a mixed-methods approach. Aim 4 will refine estimates of sample size. Finally, Aim 5 will determine the costs of ascertaining outcomes and estimate per-participant costs for the full-scale trial. The pilot study will produce data that are necessary and sufficient to inform the planning of a full-scale trial comparing CTD and CTZ and will advance the development of methods for pragmatic trials.

Conditions

Hypertension

Keywords

Hypertension; Thiazide diuretics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

Intervention is HCTZ prescription conversion to chlorthalidone. Intervention patients are defined as patients of physicians randomized to "intervention." All these patients will have their current prescription of hydrochlorothiazide (HCTZ) switched to an equipotent dose of Chlorthalidone. These patients can choose to decline this intervention, and will be followed for 9 months with no other intervention to observe primary and secondary outcomes.

Group Type: ACTIVE_COMPARATOR

HCTZ prescription conversion to chlorthalidone

Intervention Type: BEHAVIORAL

The intervention is simply a prescription conversion and the main outcome is whether or not patients accept the conversion and treatment with chlorthalidone.

Usual Care

Usual care patients are defined as patients of physicians randomized to "usual care." All these patients will keep their current prescription for HCTZ and work with their physician like normal. These patients will be followed for 9 months with no intervention to compare primary and secondary outcomes to the intervention group.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

HCTZ prescription conversion to chlorthalidone

The intervention is simply a prescription conversion and the main outcome is whether or not patients accept the conversion and treatment with chlorthalidone.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Adults 18 years and older
• Hypertension diagnosis (ICD-9 401.x)
• Current prescription for hydrochlorothiazide (HCTZ), 12.5-50 mg/day as a single-agent (not part of a fixed-dose combination drug)
• No history of intolerance to chlorthalidone (CTD)
• No known low levels of sodium (<135 mEg/L (milliequivalents per liter)) or potassium (<3.5 mEg/L)
• English speaking

Exclusion Criteria

• Physician deems patient inappropriate for switching HCTZ to CTD
• Patient refuses the switch prior to intervention

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Kaiser Permanente

OTHER

Sponsor Role: collaborator

HealthPartners Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karen L Margolis, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

HealthPartners Institute

Stephen P Fortmann, MD

Role: PRINCIPAL_INVESTIGATOR

Kaiser Permanente

Locations

HealthPartners Institute for Education and Research

Bloomington, Minnesota, United States

Kaiser Permanente Center for Health Research

Portland, Oregon, United States

Countries

United States

Other Identifiers

R34HL119790

Identifier Type: NIH

Identifier Source: org_study_id

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