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N-of-1 Trials In Children With Hypertension (NICHE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03461003
Recruitment Status : Completed
First Posted : March 9, 2018
Last Update Posted : May 4, 2021
Information provided by (Responsible Party):
Joyce Philip Samuel, The University of Texas Health Science Center, Houston

Brief Summary:
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. This trial will 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.

Condition or disease Intervention/treatment Phase
Pediatric Hypertension Other: NICHE method Other: Usual care Drug: Amlodipine Drug: Lisinopril Drug: Hydrochlorothiazide Drug: Losartan Phase 4

Detailed Description:

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 test whether the n-of-1 trial approach is superior to usual care in normalizing blood pressure while minimizing exposure to compliance-reducing side effects.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Clinical Trial of the N-of-1 Approach in Children With Hypertension
Actual Study Start Date : April 2, 2018
Actual Primary Completion Date : November 14, 2020
Actual Study Completion Date : May 2, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: NICHE method
In the NICHE method, antihypertensive therapy will be chosen using an n-of-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.
Other: 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.

Drug: Amlodipine
Calcium-channel blocker; antihypertensive

Drug: Lisinopril
Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive

Drug: Hydrochlorothiazide
Thiazide diuretic; antihypertensive

Drug: Losartan
Angiotensin II receptor blocker (ARB); antihypertensive

Active Comparator: Usual Care
No protocol will be introduced to standardize BP management in the control arm.
Other: Usual care
Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.

Primary Outcome Measures :
  1. Ambulatory blood pressure (BP) control [ Time Frame: 6 months from enrollment ]
    Normal ambulatory blood pressure by American Heart Association criteria

Secondary Outcome Measures :
  1. Ambulatory BP reduction from baseline [ Time Frame: 6 months ]
    Wake mean systolic BP (baseline) minus wake mean systolic BP (6 months)

  2. Side effect experience [ Time Frame: 6 months ]
    Questionnaire regarding overall experience with side effects on current medication

  3. Cost-effectiveness [ Time Frame: 6 months ]
    Evaluate the cost-effectiveness of the N-of-1 trial relative to usual care expressed as the incremental health system costs per additional normotensive child. Hypothesis: The N-of-1 trial will be deemed cost effective if it leads to either an increase in BP control without an increase in health system costs, a reduction in costs without a decrease in BP control, or both a reduction in costs with BP control improvement.

Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03461003

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United States, Texas
The University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
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Principal Investigator: Joyce P. Samuel, MD, MS The University of Texas Health Science Center, Houston
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Responsible Party: Joyce Philip Samuel, Assistant Professor of Pediatrics, The University of Texas Health Science Center, Houston Identifier: NCT03461003    
Other Study ID Numbers: HSC-MS-17-1014
First Posted: March 9, 2018    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Cardiotonic Agents
Protective Agents