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

November 9, 2018 updated by: Joyce Philip Samuel, The University of Texas Health Science Center, Houston

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas at Houston Medical School; Pediatric Nephrology and Hypertension Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

9 years to 22 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: 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.
Other Names:
  • Angiotensin-converting enzyme inhibitor
Drug: Amlodipine
Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
Other Names:
  • Dihydropyridine calcium channel blocker
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
Other Names:
  • Thiazide diuretic
Active Comparator: 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.
Drug: 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.
Other Names:
  • Angiotensin-converting enzyme inhibitor
Drug: Amlodipine
Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
Other Names:
  • Dihydropyridine calcium channel blocker
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
Other Names:
  • Thiazide diuretic
Active Comparator: 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.
Drug: 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.
Other Names:
  • Angiotensin-converting enzyme inhibitor
Drug: Amlodipine
Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
Other Names:
  • Dihydropyridine calcium channel blocker
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
Other Names:
  • Thiazide diuretic
Active Comparator: 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.
Drug: 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.
Other Names:
  • Angiotensin-converting enzyme inhibitor
Drug: Amlodipine
Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
Other Names:
  • Dihydropyridine calcium channel blocker
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
Other Names:
  • Thiazide diuretic
Active Comparator: 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.
Drug: 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.
Other Names:
  • Angiotensin-converting enzyme inhibitor
Drug: Amlodipine
Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
Other Names:
  • Dihydropyridine calcium channel blocker
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
Other Names:
  • Thiazide diuretic
Active Comparator: 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.
Drug: 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.
Other Names:
  • Angiotensin-converting enzyme inhibitor
Drug: Amlodipine
Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
Other Names:
  • Dihydropyridine calcium channel blocker
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
Other Names:
  • Thiazide diuretic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Health Science Center, Houston

Investigators

  • Principal Investigator: Joyce P Samuel, MD, MS, University of Texas at Houston Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

April 3, 2015

First Submitted That Met QC Criteria

April 8, 2015

First Posted (Estimate)

April 9, 2015

Study Record Updates

Last Update Posted (Actual)

November 15, 2018

Last Update Submitted That Met QC Criteria

November 9, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSC-MS-13-0287
  • 5KL2TR000370 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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