title: Comparative effectiveness of antihypertensive treatment for older children with primary hypertension: study protocol for a series of n-of-1 randomized trials.
abstract: BACKGROUND
  Children are increasingly being diagnosed with primary hypertension. The absence of comparative effectiveness research of antihypertensive medications in children has contributed to considerable differences in prescribing practices among physicians treating children with primary hypertension. Even if parallel-group trials had established a best overall choice for most of these children, the best medication for an individual may differ from the best overall medication.
  
  
  METHODS
  This project consists of a series of systematically administered n-of-1 trials among older children to verify the need for ongoing antihypertensive treatment and, if so, to identify the preferred single drug therapy from among the three major classes of drugs commonly used for primary hypertension (angiotensin-converting enzyme inhibitors, calcium channel blockers, and diuretics). We will determine whether one of these is the preferred therapy for the great majority of patients. The "preferred" therapy is the drug which produces normal ambulatory blood pressure, with the greatest reduction in blood pressure without unacceptable side effects. We will recruit 50 patients from the Houston Pediatric and Adolescent Hypertension Program clinic. For each patient, the three drugs will be prescribed in random order and each drug will be taken for 2 weeks. The effectiveness of each therapy will be measured with 24-h ambulatory blood pressure monitoring, and tolerability will be assessed using a side effect questionnaire. Participants will rotate through treatment periods, repeating drugs and adjusting doses until the preferred therapy is identified. In assessing whether one of the medications is most effective for the majority of subjects, the primary outcome will be the percentage of participants for whom each drug is selected as the preferred therapy. We hypothesize that no drug will be selected for the great majority of the subjects, a finding that would support consideration of clinical use of n-of-1 trials. Secondary analyses will explore whether patient characteristics predict which medication will be selected as a preferred drug.
  
  
  CONCLUSIONS
  This study will help optimize care of participating patients and provide evidence regarding the usefulness of n-of-1 trials in identifying appropriate treatment for children with hypertension and potentially other disorders.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT02412761 (registered 4/8/2015).
authors.affiliation: Division of Pediatric Nephrology and Hypertension, University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, 6431 Fannin, MSB 3.121, Houston, Texas, 77030, USA. joyce.p.samuel@uth.tmc.edu.
authors.forename: Joyce P
authors.initials: JP
authors.lastname: Samuel
authors.affiliation: Division of Pediatric Nephrology and Hypertension, University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, 6431 Fannin, MSB 3.121, Houston, Texas, 77030, USA. Joshua.A.Samuels@uth.tmc.edu.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Samuels
authors.affiliation: UTHealth McGovern Medical School, Houston, Texas, USA. Lauren.E.Brooks@uth.tmc.edu.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Brooks
authors.affiliation: Division of Pediatric Nephrology and Hypertension, University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, 6431 Fannin, MSB 3.121, Houston, Texas, 77030, USA. Cynthia.Bell@uth.tmc.edu.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Bell
authors.affiliation: Division of Pediatric Nephrology and Hypertension, University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, 6431 Fannin, MSB 3.121, Houston, Texas, 77030, USA. Claudia.Pedroza@uth.tmc.edu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pedroza
authors.affiliation: Division of Renal Diseases and Hypertension, UTHealth McGovern Medical School, Houston, Texas, USA. Donald.A.Molony@uth.tmc.edu.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Molony
authors.affiliation: Division of Pediatric Nephrology and Hypertension, University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School, 6431 Fannin, MSB 3.121, Houston, Texas, 77030, USA. Jon.E.Tyson@uth.tmc.edu.
authors.forename: Jon E
authors.initials: JE
authors.lastname: Tyson
mesh_terms: D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002648:Child; D002985:Clinical Protocols; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics