Trial Outcomes & Findings for N-of-1 Trials In Children With Hypertension (NCT NCT03461003)
NCT ID: NCT03461003
Last Updated: 2022-09-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
49 participants
Primary outcome timeframe
6 months from enrollment
Results posted on
2022-09-09
Participant Flow
Participant milestones
| Measure |
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
26
|
|
Overall Study
Received Intervention
|
21
|
22
|
|
Overall Study
Completed 6-month Follow up
|
18
|
23
|
|
Overall Study
COMPLETED
|
18
|
23
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
| Measure |
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
1
|
Baseline Characteristics
Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm
Baseline characteristics by cohort
| Measure |
NICHE Method
n=23 Participants
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
n=26 Participants
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
Total
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
15.9 years
n=23 Participants
|
15.9 years
n=26 Participants
|
15.9 years
n=49 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=23 Participants
|
7 Participants
n=26 Participants
|
16 Participants
n=49 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=23 Participants
|
19 Participants
n=26 Participants
|
33 Participants
n=49 Participants
|
|
Race/Ethnicity, Customized
Hispanic (black or white)
|
17 Participants
n=23 Participants
|
18 Participants
n=26 Participants
|
35 Participants
n=49 Participants
|
|
Race/Ethnicity, Customized
White (non-Hispanic)
|
1 Participants
n=23 Participants
|
1 Participants
n=26 Participants
|
2 Participants
n=49 Participants
|
|
Race/Ethnicity, Customized
Black (non-Hispanic)
|
5 Participants
n=23 Participants
|
6 Participants
n=26 Participants
|
11 Participants
n=49 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=23 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=49 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=23 Participants
|
1 Participants
n=26 Participants
|
1 Participants
n=49 Participants
|
|
Region of Enrollment
United States
|
23 participants
n=23 Participants
|
26 participants
n=26 Participants
|
49 participants
n=49 Participants
|
|
Primary language of parent
English
|
11 Participants
n=23 Participants
|
13 Participants
n=26 Participants
|
24 Participants
n=49 Participants
|
|
Primary language of parent
Spanish
|
12 Participants
n=23 Participants
|
13 Participants
n=26 Participants
|
25 Participants
n=49 Participants
|
|
Clinic Site
Multidisciplinary HTN clinic
|
12 Participants
n=23 Participants
|
14 Participants
n=26 Participants
|
26 Participants
n=49 Participants
|
|
Clinic Site
County based clinic
|
11 Participants
n=23 Participants
|
12 Participants
n=26 Participants
|
23 Participants
n=49 Participants
|
|
Hypertension type
Primary
|
17 Participants
n=23 Participants
|
22 Participants
n=26 Participants
|
39 Participants
n=49 Participants
|
|
Hypertension type
Secondary
|
6 Participants
n=23 Participants
|
4 Participants
n=26 Participants
|
10 Participants
n=49 Participants
|
|
Mean 24-hour ambulatory blood pressure at baseline (without medication)
Systolic blood pressure
|
130 mm Hg
n=22 Participants • Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm
|
130 mm Hg
n=24 Participants • Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm
|
130 mm Hg
n=46 Participants • Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm
|
|
Mean 24-hour ambulatory blood pressure at baseline (without medication)
Diastolic blood pressure
|
76 mm Hg
n=22 Participants • Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm
|
76 mm Hg
n=24 Participants • Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm
|
76 mm Hg
n=46 Participants • Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm
|
|
BMI percentile for gender and age
|
96.8 percentile
n=23 Participants
|
95.8 percentile
n=26 Participants
|
96 percentile
n=49 Participants
|
|
BMI categories
Underweight
|
0 Participants
n=23 Participants
|
0 Participants
n=26 Participants
|
0 Participants
n=49 Participants
|
|
BMI categories
Health weight
|
4 Participants
n=23 Participants
|
6 Participants
n=26 Participants
|
10 Participants
n=49 Participants
|
|
BMI categories
Overweight
|
6 Participants
n=23 Participants
|
6 Participants
n=26 Participants
|
12 Participants
n=49 Participants
|
|
BMI categories
Obese
|
13 Participants
n=23 Participants
|
14 Participants
n=26 Participants
|
27 Participants
n=49 Participants
|
|
Number of participants with Chronic Kidney Disease
|
5 Participants
n=23 Participants
|
3 Participants
n=26 Participants
|
8 Participants
n=49 Participants
|
|
Number of participants with Diabetes Mellitus
|
2 Participants
n=23 Participants
|
2 Participants
n=26 Participants
|
4 Participants
n=49 Participants
|
|
Number of participants with Proteinuria
|
2 Participants
n=23 Participants
|
3 Participants
n=26 Participants
|
5 Participants
n=49 Participants
|
|
Number of participants who avoid calcium channel blocker
|
0 Participants
n=23 Participants
|
1 Participants
n=26 Participants
|
1 Participants
n=49 Participants
|
PRIMARY outcome
Timeframe: 6 months from enrollmentBlood 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.
Outcome measures
| Measure |
NICHE Method
n=18 Participants
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
n=23 Participants
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months
Controlled
|
8 Participants
|
8 Participants
|
|
Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months
Uncontrolled
|
10 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: baseline, 6 monthsPopulation: One patient in each arm was missing a baseline ambulatory blood pressure monitoring (ABPM), so change from baseline could not be calculated for each of those participants
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.
Outcome measures
| Measure |
NICHE Method
n=17 Participants
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
n=22 Participants
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Change in Mean 24-hour Ambulatory Systolic Blood Pressure
|
-10.6 mmHg
Standard Deviation 9.301
|
-5.1 mmHg
Standard Deviation 9.586
|
SECONDARY outcome
Timeframe: baseline, 6 monthsPopulation: One patient in each arm was missing a baseline ambulatory blood pressure monitoring (ABPM), so change from baseline could not be calculated for each of those participants
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.
Outcome measures
| Measure |
NICHE Method
n=17 Participants
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
n=22 Participants
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Change in Mean Wake Ambulatory Systolic Blood Pressure
|
-10.5 mmHg
Standard Deviation 7.747
|
-6.2 mmHg
Standard Deviation 10.123
|
SECONDARY outcome
Timeframe: from baseline to 6 monthsPopulation: Data were not collected from 5 participants in the NICHE method arm, and data were not collected from 5 participants in the Usual Care arm
Outcome measures
| Measure |
NICHE Method
n=13 Participants
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
n=18 Participants
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: from month 5 to month 6Population: Data were not collected for 3 participants in the NICHE method arm.
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.
Outcome measures
| Measure |
NICHE Method
n=15 Participants
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
n=23 Participants
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Number of Participants Who Self-reported Adherence to Intervention
|
5 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Data were not collected for 4 participants in the NICHE method arm. Data were not collected for 2 participants in the Usual Care arm.
Patient satisfaction is scored from 0 to 10, where 0 is the worst health care possible and 10 is the best health care possible.
Outcome measures
| Measure |
NICHE Method
n=14 Participants
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
n=21 Participants
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Patient Satisfaction With Intervention as Assessed by a Survey
|
9.929 score on a scale
Standard Deviation 0.267
|
9.667 score on a scale
Standard Deviation 0.730
|
Adverse Events
NICHE Method
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Usual Care
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
NICHE Method
n=23 participants at risk
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: 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.
Amlodipine: Calcium-channel blocker; antihypertensive
Lisinopril: Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
Hydrochlorothiazide: Thiazide diuretic; antihypertensive
Losartan: Angiotensin II receptor blocker (ARB); antihypertensive
|
Usual Care
n=26 participants at risk
No protocol will be introduced to standardize BP management in the control arm.
Usual care: Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
|
|---|---|---|
|
Gastrointestinal disorders
Dizziness
|
0.00%
0/23 • 6 months
|
3.8%
1/26 • 6 months
|
|
General disorders
Tiredness
|
0.00%
0/23 • 6 months
|
3.8%
1/26 • 6 months
|
|
General disorders
Sleeping Poorly
|
0.00%
0/23 • 6 months
|
3.8%
1/26 • 6 months
|
Additional Information
Joyce P Samuel, MD, MS
The University of Texas Health Science Center at Houston
Phone: 713-500-6708
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place