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

NCT02412761 | Completed Results

• 2 other identifiers: HSC-MS-13-02875KL2TR000370
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Essential Hypertension

Keywords

Anti-hypertensive medications; Pediatrics; N-of-1 trial

Outcome Measures

Primary Outcomes (1)

• The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy

  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.

Study Arms (6)

Amlodipine, then HCTZ, then Lisinopril

ACTIVE COMPARATOR

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; Drug: Amlodipine; Drug: Hydrochlorothiazide

Amlodipine, then Lisinopril, then HCTZ

ACTIVE COMPARATOR

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; Drug: Amlodipine; Drug: Hydrochlorothiazide

HCTZ, then Amlodipine, then Lisinopril

ACTIVE COMPARATOR

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; Drug: Amlodipine; Drug: Hydrochlorothiazide

HCTZ, then Lisinopril, then Amlodipine

ACTIVE COMPARATOR

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; Drug: Amlodipine; Drug: Hydrochlorothiazide

Lisinopril, then Amlodipine, then HCTZ

ACTIVE COMPARATOR

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; Drug: Amlodipine; Drug: Hydrochlorothiazide

Lisinopril, then HCTZ, then Amlodipine

ACTIVE COMPARATOR

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; Drug: Amlodipine; Drug: Hydrochlorothiazide

Interventions

Lisinopril 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.

Also known as: Angiotensin-converting enzyme inhibitor

Amlodipine, then HCTZ, then Lisinopril; Amlodipine, then Lisinopril, then HCTZ; HCTZ, then Amlodipine, then Lisinopril; HCTZ, then Lisinopril, then Amlodipine; Lisinopril, then Amlodipine, then HCTZ; Lisinopril, then HCTZ, then Amlodipine

Amlodipine DRUG

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

Also known as: Dihydropyridine calcium channel blocker

Amlodipine, then HCTZ, then Lisinopril; Amlodipine, then Lisinopril, then HCTZ; HCTZ, then Amlodipine, then Lisinopril; HCTZ, then Lisinopril, then Amlodipine; Lisinopril, then Amlodipine, then HCTZ; Lisinopril, then HCTZ, then Amlodipine

Hydrochlorothiazide 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

Also known as: Thiazide diuretic

Amlodipine, then HCTZ, then Lisinopril; Amlodipine, then Lisinopril, then HCTZ; HCTZ, then Amlodipine, then Lisinopril; HCTZ, then Lisinopril, then Amlodipine; Lisinopril, then Amlodipine, then HCTZ; Lisinopril, then HCTZ, then Amlodipine

Eligibility Criteria

• Age: 9 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

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

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 26746195 BACKGROUND

• 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.

  PMID: 30842257 DERIVED

MeSH Terms

Conditions

Essential Hypertension

Interventions

Lisinopril; Angiotensin-Converting Enzyme Inhibitors; Amlodipine; Hydrochlorothiazide; Sodium Chloride Symporter Inhibitors

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Membrane Transport Modulators; Diuretics; Natriuretic Agents; Physiological Effects of Drugs

Results Point of Contact

• Title: Joyce P. Samuel, MD, MS
• Organization: The University of Texas Health Science Center at Houston

Joyce.P.Samuel@uth.tmc.edu

(713) 500-5670

Study Officials

• Joyce P Samuel, MD, MS

  University of Texas at Houston Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: April 3, 2015
• First Posted: April 9, 2015
• Study Start: June 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: November 15, 2018
• Results First Posted: November 15, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)