Essential Hypertension
Conditions
Keywords
Anti-hypertensive medications, Pediatrics, N-of-1 trial
Brief 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.
Interventions
DRUGLisinopril
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.
DRUGAmlodipine
Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
DRUGHydrochlorothiazide
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
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
9 Years to 22 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of essential hypertension * Treating physician has determined that pharmacologic therapy is necessary
Exclusion criteria
* Compelling indication to select one particular medication * Specific contraindication for any of the 3 therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy | The outcome of BP control and side effect tolerability will be assessed 2 weeks after starting each drug. Participants will be followed for an average of 10-12 weeks. | For each n-of-1 trial, the preferred drug is defined as that which produces normal ambulatory blood pressure (by pediatric Ambulatory blood pressure monitoring (ABPM) standards), with the greatest magnitude of wake mean systolic BP reduction, and without unacceptable side effects. |
Countries
United States
Participant flow
Recruitment details
From June 2013 until July 2016, 55 patients were eligible based on inclusion/exclusion criteria, and 42/55 patients (76%) agreed to participate.
Pre-assignment details
Forty-two children agreed to participate. Among the 30 patients taking antihypertensive medication prior to enrollment, 20 completed an updated baseline ambulatory BP monitoring. As a result, 23% (7/30) were found to be normotensive without medication, and did not undergo an n-of-1 trial. These 7 patients were not assigned to a treatment arm.
Participants by arm
| Arm | Count |
|---|---|
| Participants Who Completed N-of-1 Trials Participants who completed the first treatment cycle in the n-of-1 trial | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Intervention (2 Weeks) | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Participants Who Completed N-of-1 Trials |
|---|---|
| Age, Continuous | 14 years |
| Region of Enrollment United States | 32 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 0 / 32 | 0 / 32 | 2 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy
For each n-of-1 trial, the preferred drug is defined as that which produces normal ambulatory blood pressure (by pediatric Ambulatory blood pressure monitoring (ABPM) standards), with the greatest magnitude of wake mean systolic BP reduction, and without unacceptable side effects.
Time frame: The outcome of BP control and side effect tolerability will be assessed 2 weeks after starting each drug. Participants will be followed for an average of 10-12 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lisinopril | The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy | 16 Participants |
| Amlodipine | The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy | 8 Participants |
| Hydrochlorothiazide | The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy | 4 Participants |