N-of-1 Trials In Children With Hypertension

NCT ID: NCT03461003

Last Updated: 2022-09-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-02

Study Completion Date

2021-05-02

Brief Summary

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The single patient (n-of-1) randomized trial is an underused approach to resolving therapeutic uncertainty by using a patient's own data to inform an individualized treatment plan. The proposed research is designed to assess whether the n-of-1 trial approach improves blood pressure control compared to usual care. This trial aims to advance learning about not only the treatment of pediatric hypertension but also the use of a neglected type of randomized trial to optimize the care of each patient.

Detailed Description

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Pediatric hypertension, a growing problem, often requires prescription of antihypertensive medication. Pediatric hypertension specialists lack an evidentiary base on which to establish definitive clinical practice guidelines for first-line therapy. Significant practice variation is an unsurprising consequence. Routine choice of the same first-line therapy for most patients with hypertension, absent testing other options, may delay correction of blood pressure for months or years. Failure to incorporate patient preferences in medical decision-making may also contribute to decreased patient satisfaction and adherence.

Large parallel-group, comparative effectiveness trials are likely not on the horizon for this population. Moreover, heterogeneity of treatment effects would minimize the generalizability of such a trial to all patients.

This is a parallel-group, randomized clinical trial to compare the n-of-1 trial approach to usual care in normalizing blood pressure while minimizing exposure to compliance-reducing side effects.

Conditions

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Pediatric Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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NICHE method

In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.

Group Type EXPERIMENTAL

NICHE method

Intervention Type OTHER

Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.

Amlodipine

Intervention Type DRUG

Calcium-channel blocker; antihypertensive

Lisinopril

Intervention Type DRUG

Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive

Hydrochlorothiazide

Intervention Type DRUG

Thiazide diuretic; antihypertensive

Losartan

Intervention Type DRUG

Angiotensin II receptor blocker (ARB); antihypertensive

Usual Care

No protocol will be introduced to standardize BP management in the control arm.

Group Type ACTIVE_COMPARATOR

Usual care

Intervention Type OTHER

Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.

Interventions

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NICHE method

Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.

Intervention Type OTHER

Usual care

Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.

Intervention Type OTHER

Amlodipine

Calcium-channel blocker; antihypertensive

Intervention Type DRUG

Lisinopril

Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive

Intervention Type DRUG

Hydrochlorothiazide

Thiazide diuretic; antihypertensive

Intervention Type DRUG

Losartan

Angiotensin II receptor blocker (ARB); antihypertensive

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* treating physician determines that pharmacologic therapy is indicated for treatment of hypertension
* ambulatory hypertension has been confirmed (off meds) within 12 months of enrollment

Exclusion Criteria

* age \< 10 years
* resistant hypertension (requiring ≥ 3 drug therapy)
* absolute contraindication or allergy to any of the tested drugs.
Minimum Eligible Age

10 Years

Maximum Eligible Age

22 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role collaborator

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

The University of Texas Health Science Center, Houston

Locations

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The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Countries

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United States

References

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Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, Zachariah JP, Urbina EM; American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young. Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension. 2014 May;63(5):1116-35. doi: 10.1161/HYP.0000000000000007. Epub 2014 Mar 3. No abstract available.

Reference Type BACKGROUND
PMID: 24591341 (View on PubMed)

Samuel JP, Bell CS, Samuels JA, Rajan C, Walton AK, Green C, Tyson JE. N-of-1 Trials vs. Usual Care in Children With Hypertension: A Pilot Randomized Clinical Trial. Am J Hypertens. 2023 Feb 13;36(2):126-132. doi: 10.1093/ajh/hpac117.

Reference Type DERIVED
PMID: 36227203 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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UL1TR003167

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-MS-17-1014

Identifier Type: -

Identifier Source: org_study_id

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