N-of-1 Trials In Children With Hypertension

NCT03461003 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: HSC-MS-17-1014UL1TR003167
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Pediatric Hypertension

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months

  Blood pressure control is when ambulatory blood pressure is normal, with normal as defined by the American Heart Association (AHA) criteria \[the AHA criteria are systolic blood pressure and diastolic blood pressure (throughout wake and sleep) less than the 95th percentile based on the patient's gender and height\]. To assess ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24-hour period.

  6 months from enrollment

Secondary Outcomes (5)

• Change in Mean 24-hour Ambulatory Systolic Blood Pressure

  baseline, 6 months

• Change in Mean Wake Ambulatory Systolic Blood Pressure

  baseline, 6 months

• Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication

  from baseline to 6 months

• Number of Participants Who Self-reported Adherence to Intervention

  from month 5 to month 6

• Patient Satisfaction With Intervention as Assessed by a Survey

  6 months

Study Arms (2)

NICHE method

EXPERIMENTAL

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.

Other: NICHE method; Drug: Amlodipine; Drug: Lisinopril; Drug: Hydrochlorothiazide; Drug: Losartan

Usual Care

ACTIVE COMPARATOR

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

Other: Usual care

Interventions

NICHE method 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.

NICHE method

Usual care OTHER

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

Usual Care

Amlodipine DRUG

Calcium-channel blocker; antihypertensive

NICHE method

Lisinopril DRUG

Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive

NICHE method

Hydrochlorothiazide DRUG

Thiazide diuretic; antihypertensive

NICHE method

Losartan DRUG

Angiotensin II receptor blocker (ARB); antihypertensive

NICHE method

Eligibility Criteria

• Age: 10 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 24591341 BACKGROUND

• 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.

  PMID: 36227203 DERIVED

MeSH Terms

Interventions

Amlodipine; Lisinopril; Hydrochlorothiazide; Losartan

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Imidazoles; Azoles; Tetrazoles

Results Point of Contact

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

joyce.samuel@uth.tmc.edu

713-500-6708

Study Officials

• Joyce P. Samuel, MD, MS

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: January 31, 2018
• First Posted: March 9, 2018
• Study Start: April 2, 2018
• Primary Completion: November 14, 2020
• Study Completion: May 2, 2021
• Last Updated: September 9, 2022
• Results First Posted: September 9, 2022

Record last verified: 2022-08

Locations

US (1)