Pediatric HypertensionPhase 4NICHENCT03461003
N-of-1 Trials In Children With Hypertension
A Phase 4 study testing NICHE method, Amlodipine and Lisinopril in people with Pediatric Hypertension, run by The University of Texas Health Science Center, Houston at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 10 to 22 years
- Conditions the study is for
- Pediatric Hypertension
- What is being tested?
- NICHE method, Amlodipine and Lisinopril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Apr 2018to 2 May 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- treating physician determines that pharmacologic therapy is indicated for treatment of hypertension
- ambulatory hypertension has been confirmed (off meds) within 12 months of enrollment
Who cannot join
- age < 10 years
- resistant hypertension (requiring ≥ 3 drug therapy)
- absolute contraindication or allergy to any of the tested drugs.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
About this study
Official title: A Randomized Clinical Trial of the N-of-1 Approach in Children With Hypertension
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.
Read the 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.
- Conditions
- Pediatric Hypertension
- Being tested
- NICHE method, Usual care, Amlodipine, Lisinopril, Hydrochlorothiazide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NICHE methodOther
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 careOther
Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects.
AmlodipineDrug
Calcium-channel blocker; antihypertensive
LisinoprilDrug
Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive
HydrochlorothiazideDrug
Thiazide diuretic; antihypertensive
LosartanDrug
Angiotensin II receptor blocker (ARB); antihypertensive
| Study group | Role | What they receive |
|---|---|---|
| NICHE method | Experimental | 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. Receives: Other: NICHE method; Drug: Amlodipine; Drug: Lisinopril; Drug: Hydrochlorothiazide; Drug: Losartan |
| Usual Care | Active comparator | No protocol will be introduced to standardize BP management in the control arm. Receives: Other: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months from enrollment
Secondary outcomes (5)
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.
Measured: baseline, 6 months
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.
Measured: baseline, 6 months
Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication
Measured: from baseline to 6 months
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.
Measured: from month 5 to month 6
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2018
- Study start2 Apr 2018
- Primary completion14 Nov 2020
- Study completion2 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pediatric HypertensionStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Principal investigator, Joyce Philip Samuel, The University of Texas Health Science Center, Houston
- Investigators
- Joyce P. Samuel, MD, MS, Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03461003
- Sponsor's protocol ID
- HSC-MS-17-1014
- Other IDs
- UL1TR003167
- Acronym
- NICHE
- Status last verified
- Aug 2022
- First submitted
- 31 Jan 2018
- Last updated
- 9 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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. No abstract available.
PubMed 24591341Samuel JP, Bell CS, Samuels JA, Rajan C, Walton AK, Green C, Tyson JE. N-of-1 Trials vs. Usual Care in Children With Hypertension: A Pilot Randomized Clinical Trial. Am J Hypertens. 2023 Feb 13;36(2):126-132. doi: 10.1093/ajh/hpac117.
PubMed 36227203
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial of the N-of-1 Approach in Children With Hypertension
- ClinicalTrials.gov ID
- NCT03461003
- Acronym / sponsor ID
- NICHE / HSC-MS-17-1014
- Conditions
- Pediatric Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Study start
- 2 Apr 2018 (actual)
- Primary completion
- 14 Nov 2020 (actual)
- Study completion
- 2 May 2021 (actual)
- First posted
- 9 Mar 2018 (actual)
- Results
- Posted 9 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NICHE method | Experimental | Other: NICHE method, Drug: Amlodipine, Drug: Lisinopril, Drug: Hydrochlorothiazide, Drug: LosartanIn 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. |
| Usual Care | Active comparator | Other: Usual careNo protocol will be introduced to standardize BP management in the control arm. |
Who may qualify
- Ages
- 10 to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- treating physician determines that pharmacologic therapy is indicated for treatment of hypertension
- ambulatory hypertension has been confirmed (off meds) within 12 months of enrollment
Key exclusion criteria (3 listed)
- age < 10 years
- resistant hypertension (requiring ≥ 3 drug therapy)
- absolute contraindication or allergy to any of the tested drugs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NICHE methodBased 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. | Other | NICHE method |
| Usual carePhysician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects. | Other | Usual Care |
| AmlodipineCalcium-channel blocker; antihypertensive | Drug | NICHE method |
| LisinoprilAngiotensin-converting-enzyme (ACE) inhibitor; antihypertensive | Drug | NICHE method |
| HydrochlorothiazideThiazide diuretic; antihypertensive | Drug | NICHE method |
| LosartanAngiotensin II receptor blocker (ARB); antihypertensive | Drug | NICHE method |
Primary outcome
Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months
Time frame: 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.
5 secondary outcomes
Change in Mean 24-hour Ambulatory Systolic Blood Pressure
Time frame: baseline, 6 months
Change in Mean Wake Ambulatory Systolic Blood Pressure
Time frame: baseline, 6 months
Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication
Time frame: from baseline to 6 months
Number of Participants Who Self-reported Adherence to Intervention
Time frame: from month 5 to month 6
Patient Satisfaction With Intervention as Assessed by a Survey
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24591341Flynn 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. No abstract available.
- Derived from this study: PubMed 36227203Samuel JP, Bell CS, Samuels JA, Rajan C, Walton AK, Green C, Tyson JE. N-of-1 Trials vs. Usual Care in Children With Hypertension: A Pilot Randomized Clinical Trial. Am J Hypertens. 2023 Feb 13;36(2):126-132. doi: 10.1093/ajh/hpac117.
Related trials for Pediatric Hypertension
Active, not recruitingPhase 2
A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension
RecruitingObservational study
Childhood-Onset Essential Hypertension Natural History Study
Hypertension, Essential Hypertension
Recruiting
Sleep Promotion and Pediatric Hypertension
Insufficient Sleep, Hypertension
RecruitingObservational study
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)
Coronavirus Infection (COVID-19), Pulmonary Arterial Hypertension
RecruitingObservational study
Optimize Pediatric OCT Imaging
Retinal Disease, Glaucoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joyce P. Samuel, MD, MS principal investigator
The University of Texas Health Science Center, Houston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing NICHE method, Amlodipine and Lisinopril in people with Pediatric Hypertension, run by The University of Texas Health Science Center, Houston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months (time frame: 6 months from enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03461003, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2022.