Trial Outcomes & Findings for Series of N-of-1 Crossover Trials of Antihypertensive Therapy in Adolescents With Essential Hypertension (NCT NCT02412761)
NCT ID: NCT02412761
Last Updated: 2018-11-15
Results Overview
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
42 participants
Primary outcome timeframe
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.
Results posted on
2018-11-15
Participant Flow
From June 2013 until July 2016, 55 patients were eligible based on inclusion/exclusion criteria, and 42/55 patients (76%) agreed to participate.
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.
Participant milestones
| Measure |
Amlodipine, Then HCTZ, Then Lisinopril
Participants first received amlodipine once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response
|
Amlodipine, Then Lisinopril, Then HCTZ
Participants first received amlodipine once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
HCTZ, Then Amlodipine, Then Lisinopril
Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
HCTZ, Then Lisinopril, Then Amlodipine
Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
Lisinopril, Then Amlodipine, Then HCTZ
Participants first received lisinopril once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
Lisinopril, Then HCTZ, Then Amlodipine
Participants first received lisinopril once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
|---|---|---|---|---|---|---|
|
First Intervention (2 Weeks)
STARTED
|
5
|
6
|
5
|
8
|
4
|
7
|
|
First Intervention (2 Weeks)
COMPLETED
|
5
|
5
|
4
|
8
|
4
|
6
|
|
First Intervention (2 Weeks)
NOT COMPLETED
|
0
|
1
|
1
|
0
|
0
|
1
|
|
Second Intervention (2 Weeks)
STARTED
|
5
|
5
|
4
|
8
|
4
|
6
|
|
Second Intervention (2 Weeks)
COMPLETED
|
5
|
5
|
4
|
8
|
4
|
6
|
|
Second Intervention (2 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Third Intervention (2 Weeks)
STARTED
|
5
|
5
|
4
|
8
|
4
|
6
|
|
Third Intervention (2 Weeks)
COMPLETED
|
5
|
5
|
4
|
8
|
4
|
6
|
|
Third Intervention (2 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Amlodipine, Then HCTZ, Then Lisinopril
Participants first received amlodipine once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response
|
Amlodipine, Then Lisinopril, Then HCTZ
Participants first received amlodipine once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
HCTZ, Then Amlodipine, Then Lisinopril
Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then lisinopril once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
HCTZ, Then Lisinopril, Then Amlodipine
Participants first received hydrochlorothiazide (HCTZ) once daily for 2 weeks, then crossed over to lisinopril once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
Lisinopril, Then Amlodipine, Then HCTZ
Participants first received lisinopril once daily for 2 weeks, then crossed over to amlodipine once daily for 2 weeks, then hydrochlorothiazide (HCTZ) once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
Lisinopril, Then HCTZ, Then Amlodipine
Participants first received lisinopril once daily for 2 weeks, then crossed over to hydrochlorothiazide (HCTZ) once daily for 2 weeks, then amlodipine once daily for 2 weeks. Subsequent treatments varied depending on individual patient response.
|
|---|---|---|---|---|---|---|
|
First Intervention (2 Weeks)
Withdrawal by Subject
|
0
|
1
|
1
|
0
|
0
|
1
|
Baseline Characteristics
Series of N-of-1 Crossover Trials of Antihypertensive Therapy in Adolescents With Essential Hypertension
Baseline characteristics by cohort
| Measure |
Participants Who Completed N-of-1 Trials
n=32 Participants
Participants who completed the first treatment cycle in the n-of-1 trial
|
|---|---|
|
Age, Continuous
|
14 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
32 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Lisinopril
n=32 Participants
Lisinopril: 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.
|
Amlodipine
n=32 Participants
Amlodipine: Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
|
Hydrochlorothiazide
n=32 Participants
Hydrochlorothiazide: 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
|
|---|---|---|---|
|
The Number of Patients for Whom Each Drug is Selected as the Preferred Therapy
|
16 Participants
|
8 Participants
|
4 Participants
|
Adverse Events
Lisinopril
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Amlodipine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Hydrochlorothiazide
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Lisinopril
n=32 participants at risk
Lisinopril: 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.
|
Amlodipine
n=32 participants at risk
Amlodipine: Initial dose: 0.1 mg/kg/dose orally, once daily (maximum initial dose 5 mg/dose). Maximum final dose: 10 mg/dose
|
Hydrochlorothiazide
n=32 participants at risk
Hydrochlorothiazide: 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
|
|---|---|---|---|
|
Investigations
Hypokalemia
|
0.00%
0/32 • 2 weeks
|
0.00%
0/32 • 2 weeks
|
6.2%
2/32 • Number of events 2 • 2 weeks
|
Additional Information
Joyce P. Samuel, MD, MS
The University of Texas Health Science Center at Houston
Phone: (713) 500-5670
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place