Series of N-of-1 Crossover Trials of Antihypertensive Therapy in Adolescents With Essential Hypertension

Not Applicable

Completed

Conditions: Essential Hypertension

Interventions: Drug: Lisinopril
Drug: Amlodipine
Drug: Hydrochlorothiazide

Registration Number: NCT02412761

Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary: Children are increasingly being diagnosed with essential hypertension and the absence of comparative effectiveness research in antihypertensive therapies has contributed to considerable differences in prescribing practices among physicians treating children with essential hypertension.

This study will consist of a series of systematically-administered n-of-1 trials among children to verify the need for ongoing antihypertensive treatment and if so, to identify the preferred single drug therapy.

Detailed Description: This is a series of systematically-administered n-of-1 trials among children with essential hypertension to verify the need for ongoing antihypertensive treatment and if so, to identify the preferred single drug therapy from among the three major classes of drugs commonly used for essential hypertension (angiotensin converting enzyme inhibitors, calcium channel blockers, and diuretics). The investigators will determine whether there is one that is preferred for the great majority of patients. The "preferred" therapy will be defined as the drug which produces normal ambulatory blood pressure, with the greatest reduction in awake mean systolic blood pressure without unacceptable side effects.

For each patient, the order of the 3 drugs will be assigned randomly and each drug will be taken for 2 weeks. The effectiveness of each drug will be measured with 24-hour ambulatory blood pressure monitoring, and tolerability will be assessed using a side effect questionnaire. Participants will rotate through treatment periods, repeating drugs and adjusting doses until the preferred therapy is identified. In assessing whether one the medications is most effective for the great majority of subjects, the primary outcome will be the percentage of participants for whom each drug is selected as the preferred therapy. Primary hypothesis: no drug will be selected for the majority of the subjects, a finding that would support consideration of clinical use of n-of-1 trials. Secondary analyses will explore whether patient characteristics predict which medication will be selected as a preferred drug.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

Inclusion Criteria

Clinical diagnosis of essential hypertension
Treating physician has determined that pharmacologic therapy is necessary

Exclusion Criteria

Compelling indication to select one particular medication
Specific contraindication for any of the 3 therapies

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Amlodipine, then HCTZ, then Lisinopril	Lisinopril	Participants first received amlodipine once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Amlodipine, then HCTZ, then Lisinopril	Amlodipine	Participants first received amlodipine once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Amlodipine, then HCTZ, then Lisinopril	Hydrochlorothiazide	Participants first received amlodipine once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Amlodipine, then Lisinopril, then HCTZ	Amlodipine	Participants first received amlodipine once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Amlodipine, then Lisinopril, then HCTZ	Lisinopril	Participants first received amlodipine once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Amlodipine, then Lisinopril, then HCTZ	Hydrochlorothiazide	Participants first received amlodipine once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
HCTZ, then Amlodipine, then Lisinopril	Lisinopril	Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
HCTZ, then Amlodipine, then Lisinopril	Amlodipine	Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
HCTZ, then Amlodipine, then Lisinopril	Hydrochlorothiazide	Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
HCTZ, then Lisinopril, then Amlodipine	Lisinopril	Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
HCTZ, then Lisinopril, then Amlodipine	Amlodipine	Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
HCTZ, then Lisinopril, then Amlodipine	Hydrochlorothiazide	Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Lisinopril, then Amlodipine, then HCTZ	Lisinopril	Participants first received lisinopril once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Lisinopril, then Amlodipine, then HCTZ	Hydrochlorothiazide	Participants first received lisinopril once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Lisinopril, then HCTZ, then Amlodipine	Amlodipine	Participants first received lisinopril once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Lisinopril, then Amlodipine, then HCTZ	Amlodipine	Participants first received lisinopril once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Lisinopril, then HCTZ, then Amlodipine	Lisinopril	Participants first received lisinopril once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
Lisinopril, then HCTZ, then Amlodipine	Hydrochlorothiazide	Participants first received lisinopril once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.

Primary Outcome Measures

Name	Time	Method
The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy	The outcome of BP control and side effect tolerability will be assessed 2 weeks after starting each drug. Participants will be followed for an average of 10-12 weeks.	For each n-of-1 trial, the preferred drug is defined as that which produces normal ambulatory blood pressure (by pediatric Ambulatory blood pressure monitoring (ABPM) standards), with the greatest magnitude of wake mean systolic BP reduction, and without unacceptable side effects.

Secondary Outcome Measures