Hypertensive Ambulatory Trial to Compare the Efficacy of HCTZ and Lisinopril (1HAT)

Series of Single Patient Trials Comparing the Efficacy Between the Most Commonly Prescribed Thiazide Diuretic in the US, Hydrochlorothiazide, and Lisinopril for the Treatment of Stage 1 Hypertension.

The purpose of this trial is to evaluate if an objective clinical decision of anti-hypertensive therapy can be made using an N-of-1 (single patient) trial design.

Study Overview

• Status: Completed
• Conditions: Hypertension; Hypertension, Grade 1; Hypertension Treatment; N of 1 Study Design
• Intervention / Treatment: Drug: Lisinopril; Drug: Hydrochlorothiazide

Detailed Description

Personalized medicine involves choosing the optimal treatment for a patient based on data gathered by the physician that is specific to that individual. The N-of-1 or single patient trial is a study design motivated by the new era of personalized medicine. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends a personalized medicine approach to hypertensive drug class choice based on compelling indications. However, the hypertensive decision algorithm is limited. With the advent of new technology the amount of data available to a physician has grown substantially improving the robustness of surveying a more complete picture of the patient's health care status. Medicine is quickly becoming data intensive with new technology decreasing the cost of data collection and analysis.

The typical standard care for patients with stage 1 hypertension first involves a non-pharmacological modification of lifestyle changes. Health care providers diagnose hypertension when the blood pressure is persistently elevated after three to six visits over a several month period. JNC 7 recommends thiazide-type diuretics for Stage I hypertension for most patients. In the United States, this recommendation results in most patients being given a dose of hydrochlorothiazide (HCTZ) at 12.5 to 25 mg per day. A patient would then return for follow-up and would be prescribed a few month supply of an antihypertensive medication (e.g. HCTZ or lisinopril). The choice of treatment by the physician is based on JNC 7 guidelines, patient's risk factors, and a provider's experience.

The objective of this trial will be to evaluate if an objective clinical decision of anti-hypertensive therapy can be made using an N-of-1 (single patient) trial design. In this study we propose to do a series of N-of-1 trials in patients with stage 1 hypertension who will be randomized to alternating courses of HCTZ and lisinopril.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Grade 1 Hypertension
• Treatment naïve
• GFR > 60 within previous 3 months
• Urinary microalbumin level normal during previous 3 months

Exclusion Criteria:

• Pregnancy (Fetal morbidity and mortality may occur with the use of ACE inhibitors.)
• Uncontrolled Hyperthyroidism
• Sleep Apnea
• Primary Aldosteronism
• Renovascular Disease
• Cushing's Syndrome or steroid therapy
• No evidence of end organ damage
• EKG with evidence of LVH within previous 3 months
• Collagen Vascular Disease
• Current Smoker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lisinopril	Drug: Lisinopril; Lisinopril 10 mg oral, once daily for four week cycle and a 2 week cycle; Other Names: Prinivil; Zestril; ACE inhibitor
Active Comparator: Hydrochlorothiazide	Drug: Hydrochlorothiazide; Hydrochlorothiazide 25 mg oral, once daily for 4 week cycle and a 2 week cycle; Other Names: HCTZ; HydroDIURIL; Aquazide H; Carozide; Diaqua; Esidrix; Ezide; Hydro Par; Hydrocot; Hydrokraft; Loqua; Oretic; Thiazide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood pressure control defined as 24-hour ambulatory systolic and diastolic pressure average below 135/85 mmHg.	After 14 week study period with assessment of patient specific data

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure (BP) load, treatment of non-dippers, side effects, and compliance.	BP load is defined as the percentage of ambulatory systolic and diastolic pressure exceeding 140 mmHg and 90 mmHg during the daytime and 120 mmHg and 80 mmHg during sleep. Systolic BP load averages 9-25% depending on age. While diastolic BP load averages 3-4%. Failure of BP to fall by at least 10 percent during sleep will define a non-dipper. Extreme dipping will be defined by a nocturnal BP decline of greater than 20 percent with a large morning increase in BP.	After 14 week study period with assessment of patient specific data

Collaborators and Investigators

• Sponsor: Scripps Translational Science Institute
• Investigators: Principal Investigator: Bradley Patay, MD, Scripps Clinic

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: December 9, 2010
• First Submitted That Met QC Criteria: December 10, 2010
• First Posted (Estimate): December 13, 2010

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 19, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: hypertension; Blood Pressure control; hypertension treatment; antihypertensive; N of 1 study
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Natriuretic Agents; Cardiotonic Agents; Membrane Transport Modulators; Diuretics; Sodium Chloride Symporter Inhibitors; Hydrochlorothiazide; Lisinopril; Angiotensin-Converting Enzyme Inhibitors
• Other Study ID Numbers: STSI 10-5486