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

The University of Texas System (UT)

Status: Completed

Conditions: Essential Hypertension

Treatments: Drug: Amlodipine; Drug: Hydrochlorothiazide; Drug: Lisinopril

Study type: Interventional

Funder types: Other

Identifiers

NCT02412761

5KL2TR000370 (U.S. NIH Grant/Contract)

HSC-MS-13-0287

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 9 to 22 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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42 participants in 6 patient groups

Amlodipine, then HCTZ, then Lisinopril

Active Comparator group

Description:

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.

Treatment:

Drug: Lisinopril

Drug: Hydrochlorothiazide

Drug: Amlodipine

Amlodipine, then Lisinopril, then HCTZ

Active Comparator group

Description:

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.

Treatment:

Drug: Lisinopril

Drug: Hydrochlorothiazide

Drug: Amlodipine

HCTZ, then Amlodipine, then Lisinopril

Active Comparator group

Description:

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.

Treatment:

Drug: Lisinopril

Drug: Hydrochlorothiazide

Drug: Amlodipine

HCTZ, then Lisinopril, then Amlodipine

Active Comparator group

Description:

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.

Treatment:

Drug: Lisinopril

Drug: Hydrochlorothiazide

Drug: Amlodipine

Lisinopril, then Amlodipine, then HCTZ

Active Comparator group

Description:

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.

Treatment:

Drug: Lisinopril

Drug: Hydrochlorothiazide

Drug: Amlodipine

Lisinopril, then HCTZ, then Amlodipine

Active Comparator group

Description:

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.

Treatment:

Drug: Lisinopril

Drug: Hydrochlorothiazide

Drug: Amlodipine