Treating Hypertension in Children With n-of-1 Trials

Abstract

Objectives: Clinicians prescribe antihypertensive medication to children with primary hypertension, but without data to define a particular choice as first-line therapy. A one-size-fits-all approach may not be appropriate for these patients. Our aim was to develop a personalized approach to hypertension treatment, using repeated ambulatory blood pressure monitoring (ABPM) in n-of-1 trials (single-patient randomized crossover trials).

Methods: Children undergoing hypertension management at a single pediatric referral center were offered participation in an n-of-1 trial with repeated ABPM to compare 3 commonly used medications. The medication producing the greatest blood pressure reduction, and without unacceptable side effects, was selected as the preferred therapy for the individual.

Results: Forty-two children agreed to participate; 7 were normotensive without medication; and 3 failed to complete one treatment cycle. Of the remaining 32 patients, lisinopril was preferred for 16, amlodipine for 8, hydrochlorothiazide for 4, and 4 had uncontrolled blood pressure on maximum doses of monotherapy. In conservative Bayesian analyses, the proportion of patients who preferred lisinopril was 49% (95% credible interval [CrI]: 32% to 69%), 24% (95% CrI: 12% to 41%) preferred amlodipine, and 12% (95% CrI: 4% to 26%) preferred hydrochlorothiazide. The preferred therapy for the majority (67%) of African American participants was lisinopril. Unacceptable side effects were reported in 24% of assessments for hydrochlorothiazide, 16% for lisinopril, and 13% for amlodipine.

Conclusions: No single medication was preferred for more than half of hypertensive children. n of-1 trials with repeated ABPM may promote better informed and individualized decisions in pediatric hypertension management.

Trial registration: ClinicalTrials.gov NCT02412761.

Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Copyright © 2019 by the American Academy of Pediatrics.

Figures

FIGURE 1

n-of-1 trial design. aIf normal ambulatory BP is achieved in cycle 1, continue the same dose. If ambulatory hypertension persists in cycle 1, increase doses according to Supplemental Table 5. bIf maximal dosing recommendations prevent further dose increase of monotherapy, the n-of-1 trial is considered complete, and combination therapy is initiated in the Pediatric Hypertension Clinic. cIf normal ambulatory BP is now achieved after increased dose in the previous cycle, continue the increased dose for an additional cycle. If ambulatory hypertension persists, the dose for the next cycle is increased further according to Supplemental Table 6.

FIGURE 2

CONSORT flow diagram. CONSORT, Consolidated Standards of Reporting Trials: extension for reporting n-of-1 trials 2015.

FIGURE 3

Primary outcome. Probability that each medication would be selected as the preferred therapy.

FIGURE 4

Effect of study on medication among the 30 patients treated before study. Comparison of n-of-1 defined preferred medication with pretrial therapy.

FIGURE 5

BP at baseline (no medication) and with each treatment. Mean awake SBP as a function of treatment and time.