N-of-1 Trials In Children With Hypertension

Pediatric Hypertension Clinical Trial

— NICHE  

Official title:

A Randomized Clinical Trial of the N-of-1 Approach in Children With Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03461003
• Other study ID #: HSC-MS-17-1014
• Secondary ID: UL1TR003167
• Status: Completed
• Phase: Phase 4
• Start date: April 2, 2018
• Est. completion date: May 2, 2021

Study information

• Verified date: August 2022
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: May 2, 2021
• Est. primary completion date: November 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 22 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension
• Pediatric Hypertension

Intervention

Other:
• NICHE method
Based on underlying comorbidities at enrollment, patients will be assigned to either an unrestricted protocol (amlodipine versus lisinopril) or a restricted protocol (losartan versus lisinopril). Two drugs are tested in randomized order. Failure to achieve BP control at maximum doses of the first two drugs will result in augmentation with a diuretic (hydrochlorothiazide). BP control is assessed with 24 hour ambulatory monitoring at the end of each 2 week treatment period. Side effect tolerability is assessed with a questionnaire.
• Usual care
Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.

Drug:
• Amlodipine
Calcium-channel blocker; antihypertensive
• Lisinopril
Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
• Hydrochlorothiazide
Thiazide diuretic; antihypertensive
• Losartan
Angiotensin II receptor blocker (ARB); antihypertensive

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at Houston	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	National Center for Advancing Translational Science (NCATS)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, Zachariah JP, Urbina EM; American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young. Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension. 2014 May;63(5):1116-35. doi: 10.1161/HYP.0000000000000007. Epub 2014 Mar 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months	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.	6 months from enrollment
Secondary	Change in Mean 24-hour Ambulatory Systolic Blood Pressure	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.	baseline, 6 months
Secondary	Change in Mean Wake Ambulatory Systolic Blood Pressure	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.	baseline, 6 months
Secondary	Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication		from baseline to 6 months
Secondary	Number of Participants Who Self-reported Adherence to Intervention	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.	from month 5 to month 6
Secondary	Patient Satisfaction With Intervention as Assessed by a Survey	Patient satisfaction is scored from 0 to 10, where 0 is the worst health care possible and 10 is the best health care possible.	6 months