Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| UL1TR003167 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Center for Advancing Translational Sciences (NCATS) | NIH |
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Usual Care | Active Comparator | No protocol will be introduced to standardize BP management in the control arm. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NICHE method | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Joyce P. Samuel, MD, MS | The University of Texas Health Science Center, Houston | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24591341 | Background | 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. | |
| 36227203 |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Count of Participants | Participants | 6 months from enrollment |
|
6 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Gastrointestinal disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joyce P Samuel, MD, MS | The University of Texas Health Science Center at Houston | 713-500-6708 | joyce.samuel@uth.tmc.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 26, 2019 | Oct 1, 2021 | Prot_SAP_002.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D017311 | Amlodipine |
| D017706 | Lisinopril |
| D006852 | Hydrochlorothiazide |
| D019808 | Losartan |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Usual care | Other | Physician preference will dictate choice and adjustment of antihypertensive medication, BP measurement modality, interval between visits, and assessment of side effects. |
|
| Amlodipine | Drug | Calcium-channel blocker; antihypertensive |
|
| Lisinopril | Drug | Angiotensin-converting-enzyme (ACE) inhibitor; antihypertensive |
|
| Hydrochlorothiazide | Drug | Thiazide diuretic; antihypertensive |
|
| Losartan | Drug | Angiotensin II receptor blocker (ARB); antihypertensive |
|
| 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. | baseline, 6 months |
| Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication | 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. | 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. | 6 months |
| Samuel 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Primary language of parent | Count of Participants | Participants |
|
| Clinic Site | Count of Participants | Participants |
|
| Hypertension type | Count of Participants | Participants |
|
| Mean 24-hour ambulatory blood pressure at baseline (without medication) | To assess 24-hour 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, and the median of these means is reported. | Data not collected from 1 participant in the NICHE arm and 2 participants in the usual care arm | Median | Inter-Quartile Range | mm Hg |
|
| BMI percentile for gender and age | Median | Full Range | percentile |
|
| BMI categories | Count of Participants | Participants |
|
| Number of participants with Chronic Kidney Disease | Count of Participants | Participants |
|
| Number of participants with Diabetes Mellitus | Count of Participants | Participants |
|
| Number of participants with Proteinuria | Count of Participants | Participants |
|
| Number of participants who avoid calcium channel blocker | Count of Participants | Participants |
|
| OG001 | 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. |
|
|
| 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. | 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 | Posted | Mean | Standard Deviation | mmHg | 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. | 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 | Posted | Mean | Standard Deviation | mmHg | baseline, 6 months |
|
|
|
| Secondary | Number of Participants Who Reported That Side Effects From Medication Led Them to Discontinue Medication | 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 | Posted | Count of Participants | Participants | 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. | Data were not collected for 3 participants in the NICHE method arm. | Posted | Count of Participants | Participants | 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. | Data were not collected for 4 participants in the NICHE method arm. Data were not collected for 2 participants in the Usual Care arm. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| 0 |
| 23 |
| EG001 | 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. | 0 | 26 | 0 | 26 | 3 | 26 |
| Tiredness | General disorders | Systematic Assessment |
|
| Sleeping Poorly | General disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D004151 |
| Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D013777 | Tetrazoles |
| Black (non-Hispanic) |
|
| Asian |
|
| Other |
|
| Overweight |
|
| Obese |
|