Clinical trial NCT02591628: Treatment of Hypertension In Adults With ThiaZIDES: Pragmatic Trial Pilot Study
Official title: Treatment of Hypertension In Adults With ThiaZIDES: Pragmatic Trial Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Keywords: Hypertension
Thiazide diuretics
Lead sponsor: HealthPartners Institute
Sponsor class: OTHER
Collaborators: name: Kaiser Permanente
First posted: 2015-10-29
Enrollment: 2027
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Conversion to chlorthalidone, number of patients with primary fills
timeFrame: 3 months
measure: Conversion to chlorthalidone, number of participants with secondary fills
timeFrame: 9 months
Secondary outcomes:
measure: Blood pressure
timeFrame: 9 months
measure: Hypertension drugs
timeFrame: 9 months
measure: Electrolyte levels
timeFrame: 9 months
measure: Renal function
timeFrame: 9 months
measure: Safety outcomes
timeFrame: 9 months
Other outcomes:
Locations:
city: Bloomington
country: United States
facility: HealthPartners Institute for Education and Research
state: Minnesota
city: Portland
country: United States
facility: Kaiser Permanente Center for Health Research
state: Oregon
Study officials:
affiliation: HealthPartners Institute
name: Karen L Margolis, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaiser Permanente
name: Stephen P Fortmann, MD
role: PRINCIPAL_INVESTIGATOR
References: