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

NCT ID: NCT02412761

Last Updated: 2018-11-15

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2016-07-31

Brief Summary

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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

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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.

Conditions

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Essential Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Amlodipine, then HCTZ, then 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.

Group Type ACTIVE_COMPARATOR

Lisinopril

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 10 mg/dose). Maximum final dose: 40 mg/dose or 0.6 mg/kg/dose.

Amlodipine

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose

Hydrochlorothiazide

Intervention Type DRUG

Initial dose: 1 mg/kg/dose orally, once daily (maximum initial dose 25 mg/dose). Maximum final dose: 50 mg/dose or 3 mg/kg/dose

Amlodipine, then Lisinopril, then HCTZ

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.

Group Type ACTIVE_COMPARATOR

Lisinopril

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 10 mg/dose). Maximum final dose: 40 mg/dose or 0.6 mg/kg/dose.

Amlodipine

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose

Hydrochlorothiazide

Intervention Type DRUG

Initial dose: 1 mg/kg/dose orally, once daily (maximum initial dose 25 mg/dose). Maximum final dose: 50 mg/dose or 3 mg/kg/dose

HCTZ, then Amlodipine, then 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.

Group Type ACTIVE_COMPARATOR

Lisinopril

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 10 mg/dose). Maximum final dose: 40 mg/dose or 0.6 mg/kg/dose.

Amlodipine

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose

Hydrochlorothiazide

Intervention Type DRUG

Initial dose: 1 mg/kg/dose orally, once daily (maximum initial dose 25 mg/dose). Maximum final dose: 50 mg/dose or 3 mg/kg/dose

HCTZ, then Lisinopril, then 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.

Group Type ACTIVE_COMPARATOR

Lisinopril

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 10 mg/dose). Maximum final dose: 40 mg/dose or 0.6 mg/kg/dose.

Amlodipine

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose

Hydrochlorothiazide

Intervention Type DRUG

Initial dose: 1 mg/kg/dose orally, once daily (maximum initial dose 25 mg/dose). Maximum final dose: 50 mg/dose or 3 mg/kg/dose

Lisinopril, then Amlodipine, then HCTZ

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.

Group Type ACTIVE_COMPARATOR

Lisinopril

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 10 mg/dose). Maximum final dose: 40 mg/dose or 0.6 mg/kg/dose.

Amlodipine

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose

Hydrochlorothiazide

Intervention Type DRUG

Initial dose: 1 mg/kg/dose orally, once daily (maximum initial dose 25 mg/dose). Maximum final dose: 50 mg/dose or 3 mg/kg/dose

Lisinopril, then HCTZ, then 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.

Group Type ACTIVE_COMPARATOR

Lisinopril

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 10 mg/dose). Maximum final dose: 40 mg/dose or 0.6 mg/kg/dose.

Amlodipine

Intervention Type DRUG

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose

Hydrochlorothiazide

Intervention Type DRUG

Initial dose: 1 mg/kg/dose orally, once daily (maximum initial dose 25 mg/dose). Maximum final dose: 50 mg/dose or 3 mg/kg/dose

Interventions

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Lisinopril

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 10 mg/dose). Maximum final dose: 40 mg/dose or 0.6 mg/kg/dose.

Intervention Type DRUG

Amlodipine

Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose

Intervention Type DRUG

Hydrochlorothiazide

Initial dose: 1 mg/kg/dose orally, once daily (maximum initial dose 25 mg/dose). Maximum final dose: 50 mg/dose or 3 mg/kg/dose

Intervention Type DRUG

Other Intervention Names

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Angiotensin-converting enzyme inhibitor Dihydropyridine calcium channel blocker Thiazide diuretic

Eligibility Criteria

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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
Minimum Eligible Age

9 Years

Maximum Eligible Age

22 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Texas Health Science Center, Houston

OTHER

Sponsor Role lead

Responsible Party

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Joyce Philip Samuel

Assistant Professor of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Joyce P Samuel, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Texas at Houston Medical School

Locations

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University of Texas at Houston Medical School; Pediatric Nephrology and Hypertension Clinics

Houston, Texas, United States

Site Status

Countries

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United States

References

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Samuel JP, Samuels JA, Brooks LE, Bell CS, Pedroza C, Molony DA, Tyson JE. Comparative effectiveness of antihypertensive treatment for older children with primary hypertension: study protocol for a series of n-of-1 randomized trials. Trials. 2016 Jan 8;17:16. doi: 10.1186/s13063-015-1142-y.

Reference Type BACKGROUND
PMID: 26746195 (View on PubMed)

Samuel JP, Tyson JE, Green C, Bell CS, Pedroza C, Molony D, Samuels J. Treating Hypertension in Children With n-of-1 Trials. Pediatrics. 2019 Apr;143(4):e20181818. doi: 10.1542/peds.2018-1818. Epub 2019 Mar 6.

Reference Type DERIVED
PMID: 30842257 (View on PubMed)

Other Identifiers

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5KL2TR000370

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-MS-13-0287

Identifier Type: -

Identifier Source: org_study_id

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