N-of-1 Trials In Children With Hypertension

Phase 4

Completed

Conditions: Pediatric Hypertension

Interventions: Other: Usual care
Other: NICHE method
Drug: Amlodipine
Drug: Lisinopril
Drug: Hydrochlorothiazide
Drug: Losartan

Registration Number: NCT03461003

Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary: The single patient (n-of-1) randomized trial is an underused approach to resolving therapeutic uncertainty by using a patient's own data to inform an individualized treatment plan. The proposed research is designed to assess whether the n-of-1 trial approach improves blood pressure control compared to usual care. This trial aims to advance learning about not only the treatment of pediatric hypertension but also the use of a neglected type of randomized trial to optimize the care of each patient.

Detailed Description: Pediatric hypertension, a growing problem, often requires prescription of antihypertensive medication. Pediatric hypertension specialists lack an evidentiary base on which to establish definitive clinical practice guidelines for first-line therapy. Significant practice variation is an unsurprising consequence. Routine choice of the same first-line therapy for most patients with hypertension, absent testing other options, may delay correction of blood pressure for months or years. Failure to incorporate patient preferences in medical decision-making may also contribute to decreased patient satisfaction and adherence.

Large parallel-group, comparative effectiveness trials are likely not on the horizon for this population. Moreover, heterogeneity of treatment effects would minimize the generalizability of such a trial to all patients.

This is a parallel-group, randomized clinical trial to compare the n-of-1 trial approach to usual care in normalizing blood pressure while minimizing exposure to compliance-reducing side effects.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 49

Inclusion Criteria

treating physician determines that pharmacologic therapy is indicated for treatment of hypertension
ambulatory hypertension has been confirmed (off meds) within 12 months of enrollment

Exclusion Criteria

age < 10 years
resistant hypertension (requiring ≥ 3 drug therapy)
absolute contraindication or allergy to any of the tested drugs.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Usual Care	Usual care	No protocol will be introduced to standardize BP management in the control arm.
NICHE method	NICHE method	In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.
NICHE method	Hydrochlorothiazide	In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.
NICHE method	Amlodipine	In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.
NICHE method	Lisinopril	In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.
NICHE method	Losartan	In the NICHE method, antihypertensive therapy will be chosen using an n-of-1 trial to identify the preferred therapy. Preferred therapy is defined a priori as that which produces the greatest reduction in ambulatory BP without intolerable side effects. Tested drugs will include amlodipine or losartan, lisinopril, and hydrochlorothiazide.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months	6 months from enrollment	Blood pressure control is when ambulatory blood pressure is normal, with normal as defined by the American Heart Association (AHA) criteria \[the AHA criteria are systolic blood pressure and diastolic blood pressure (throughout wake and sleep) less than the 95th percentile based on the patient's gender and height\]. To assess ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24-hour period.

Secondary Outcome Measures

Name	Time	Method
Patient Satisfaction With Intervention as Assessed by a Survey	6 months	Patient satisfaction is scored from 0 to 10, where 0 is the worst health care possible and 10 is the best health care possible.
Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication	from baseline to 6 months
Change in Mean 24-hour Ambulatory Systolic Blood Pressure	baseline, 6 months	To assess 24-hour mean ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24-hour period, while awake and while asleep. The mean of all recordings over the 24-hour period is calculated per participant for both baseline and 6 months, and then the mean 24-hour systolic blood pressure at 6 months minus the mean 24-hour systolic blood pressure at baseline is calculated per participant. The average difference is reported, with a negative value indicating a reduction in blood pressure over time.
Number of Participants Who Self-reported Adherence to Intervention	from month 5 to month 6	Adherence is reported as the number of participants who self-reported at the 6-month visit that they had not missed any doses of their medication in the preceding month.
Change in Mean Wake Ambulatory Systolic Blood Pressure	baseline, 6 months	To assess mean wake ambulatory blood pressure, participants wear a 24-hour blood pressure monitor, which records blood pressure at regular intervals throughout a 24 hour period, throughout wake and sleep. The mean of all recordings that occur while the participant is awake during the 24-hour period is calculated for both baseline and 6 months, and then the mean wake systolic blood pressure at 6 months minus the mean wake systolic blood pressure at baseline is calculated per participant. The average difference is reported, with a negative value indicating a reduction in blood pressure over time.