Series of N-of-1 Crossover Trials of Antihypertensive Therapy in Adolescents With Essential Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Study type: Interventional

Summary: 
      Children are increasingly being diagnosed with essential hypertension and the absence of
      comparative effectiveness research in antihypertensive therapies has contributed to
      considerable differences in prescribing practices among physicians treating children with
      essential hypertension.

      This study will consist of a series of systematically-administered n-of-1 trials among
      children to verify the need for ongoing antihypertensive treatment and if so, to identify the
      preferred single drug therapy.
    

Detailed description: 
      This is a series of systematically-administered n-of-1 trials among children with essential
      hypertension 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 essential hypertension (angiotensin converting enzyme inhibitors, calcium channel
      blockers, and diuretics). The investigators will determine whether there is one that is
      preferred for the great majority of patients. The "preferred" therapy will be defined as the
      drug which produces normal ambulatory blood pressure, with the greatest reduction in awake
      mean systolic blood pressure without unacceptable side effects.

      For each patient, the order of the 3 drugs will be assigned randomly and each drug will be
      taken for 2 weeks. The effectiveness of each drug will be measured with 24-hour 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 the
      medications is most effective for the great majority of subjects, the primary outcome will be
      the percentage of participants for whom each drug is selected as the preferred therapy.
      Primary hypothesis: no drug will be selected for the 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.
    

Intervention name(s): Lisinopril; Amlodipine; Hydrochlorothiazide
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 10 mg/dose). Maximum final dose: 40 mg/dose or 0.6 mg/kg/dose.; Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose; Initial dose: 1 mg/kg/dose orally, once daily (maximum initial dose 25 mg/dose). Maximum final dose: 50 mg/dose or 3 mg/kg/dose
Other intervention name(s): Angiotensin-converting enzyme inhibitor; Dihydropyridine calcium channel blocker; Thiazide diuretic
Intervention MeSH terms: Amlodipine; Hydrochlorothiazide; Lisinopril; Calcium Channel Blockers; Diuretics; Sodium Chloride Symporter Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Enzyme Inhibitors
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Anti-hypertensive medications; Pediatrics; N-of-1 trial