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.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Academic Medical Centers
  • Adolescent
  • Amlodipine / therapeutic use*
  • Antihypertensive Agents / therapeutic use
  • Bayes Theorem
  • Blood Pressure Determination / methods
  • Blood Pressure Monitoring, Ambulatory / methods*
  • Child
  • Cross-Over Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrochlorothiazide / therapeutic use*
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Lisinopril / therapeutic use*
  • Male
  • Patient Preference
  • Precision Medicine*
  • Texas
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Hydrochlorothiazide
  • Amlodipine
  • Lisinopril

Associated data

  • ClinicalTrials.gov/NCT02412761