Ambulatory Blood Pressure Monitoring in Children
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 6 - 18 |
| Updated: | 4/2/2016 |
| Start Date: | February 2010 |
| End Date: | May 2012 |
| Contact: | Jeffrey L. Blumer, Ph.D., M.D. |
| Email: | Jeffrey.blumer@case.edu |
| Phone: | (216) 844-3310 |
Methodological Improvement in Measuring Efficacy Outcome in Antihypertensive Trials in Children
Ambulatory Blood Pressure Monitoring (ABPM) potentially offers a superior way to screen
children for entry into antihypertensive trials, assuring that only those with true
hypertension are enrolled.10 In addition, ABPM offers a better method to measure response to
drug therapy.11-16 The ABPM device most commonly used in children (Spacelabs 90217 -
Issaquah, Washington) has not been independently validated for use in this population. In
1993, the British Hypertension Society (BHS) published a protocol for validating ABPM
devices, including guidance for validation studies in children.17 More recently, the Working
Group on Blood Pressure Monitoring of the European Society of Hypertension published
revisions to these guidelines, but did not include children in this update.18 Unfortunately,
the original BHS protocol suggests using a smaller group of children than the protocol
outlines for adults. Since BP in children is more variable than in adults, this guidance is
unlikely to be adequate for children. Hence, a large, stringent validation study needs to be
conducted in a cohort of children using the methods similar to those used to validate the
device in adults. Performance of the proposed validation study is needed to allow for the
incorporation of ABPM into clinical trial designs of anti-hypertensives in children which
will ultimately allow for more accurate identification of the hypertensive population and
determination of response to therapy along with allowing for assessment of the
chronobiologic profile of drug response over the dosing interval.9
children for entry into antihypertensive trials, assuring that only those with true
hypertension are enrolled.10 In addition, ABPM offers a better method to measure response to
drug therapy.11-16 The ABPM device most commonly used in children (Spacelabs 90217 -
Issaquah, Washington) has not been independently validated for use in this population. In
1993, the British Hypertension Society (BHS) published a protocol for validating ABPM
devices, including guidance for validation studies in children.17 More recently, the Working
Group on Blood Pressure Monitoring of the European Society of Hypertension published
revisions to these guidelines, but did not include children in this update.18 Unfortunately,
the original BHS protocol suggests using a smaller group of children than the protocol
outlines for adults. Since BP in children is more variable than in adults, this guidance is
unlikely to be adequate for children. Hence, a large, stringent validation study needs to be
conducted in a cohort of children using the methods similar to those used to validate the
device in adults. Performance of the proposed validation study is needed to allow for the
incorporation of ABPM into clinical trial designs of anti-hypertensives in children which
will ultimately allow for more accurate identification of the hypertensive population and
determination of response to therapy along with allowing for assessment of the
chronobiologic profile of drug response over the dosing interval.9
The diagnosis and treatment of hypertension remains a challenge in children and
adolescents.1 At present the diagnosis is made during medical encounters and depends on
randomly applied auscultatory or oscillometric techniques.2 These measurements are
influenced by multiple factors including diurnal variation, stress related effects (most
notably the fact that the measurement is being performed in a physician's office or clinic),
observer bias and the measurement process itself. In addition, these standard approaches
provide little information regarding blood pressure and its variability in the patients'
ambient environments.3,4 If and when a diagnosis of hypertension is made, lifestyle changes
are often prescribed. In children and adolescents these recommendations meet with mixed
results that often frustrate patients and families as well as caregivers. In most cases,
where sufficient concern exists regarding the long-term health of end organs such as the
heart, kidney, eye and brain, pharmacotherapy is recommended. Unfortunately, in these
instances drugs are prescribed with little information to guide proper, age-related dosing
or safety assessment. In studies conducted over the last decade more than half of the agents
marketed for adults with hypertension failed to demonstrate sufficient activity in children
and adolescents to meet regulatory requirements for labeling.5 While a significant amount of
this apparent ambiguity appears to be related to the design of the studies assessing the
efficacy and safety of these drugs in pediatric patients, perhaps a more significant problem
in these studies was the determination of who is actually hypertensive in the first place.
This supplement addresses this issue directly by introducing an innovative approach to the
diagnosis of hypertension in children and adolescents. Once validated, ambulatory BP
monitoring may be used to describe and model the chronobiological patterns of blood pressure
among patients who have been recently diagnosed with hypertension using standard clinical
criteria. This is a unique opportunity to assess treatment naïve patients and compare an
innovative new approach to what is currently the gold standard.
The current project is designed specifically to validate the use of ambulatory blood
pressure monitoring (ABPM) in children and adolescents so that it may be used as a clinical
tool for unambiguously making the diagnosis of hypertension in this patient population and
then be used to guide pharmacotherapeutic intervention. The use of ABPM in children was
first documented in 19916 and has subsequently been employed in children as young as 2
months of age. Despite its adjunctive use by more than 60% of pediatric nephrologists in
North America, the device currently used in the majority of pediatric practices and research
centers has never been validated in a pediatric population.
In contrast, ABPM has become a world-wide standard for monitoring blood pressure in adults
with suspected hypertension. It offers the advantages of multiple measurements of a dynamic
process over a protracted period of time and permits the evaluation of diurnal patterns and
nocturnal disease. It also offers distinct advantages in monitoring patients in their
natural environment without observer bias while permitting objective assessment of apparent
drug resistance and hypotensive events that might occur on therapy. Finally, ABPM
measurements have been demonstrated to better correlate with cardiovascular morbidity and
mortality than casual measurements.7 They also correlate with end organ damage in children.8
Performance of the proposed validation study is needed to allow for incorporation of ABPM
into clinical trial designs related to the diagnosis and treatment of hypertension in
children. ABPM will ultimately allow for more accurate determination of response to therapy
and asses the chronobiologic profile of drug response over the dosing interval. Of the
devices currently marketed, the Spacelabs 90217 offers the range of cuff sizes required by
the pediatric population. Thus, it is this monitor that will be validated.
adolescents.1 At present the diagnosis is made during medical encounters and depends on
randomly applied auscultatory or oscillometric techniques.2 These measurements are
influenced by multiple factors including diurnal variation, stress related effects (most
notably the fact that the measurement is being performed in a physician's office or clinic),
observer bias and the measurement process itself. In addition, these standard approaches
provide little information regarding blood pressure and its variability in the patients'
ambient environments.3,4 If and when a diagnosis of hypertension is made, lifestyle changes
are often prescribed. In children and adolescents these recommendations meet with mixed
results that often frustrate patients and families as well as caregivers. In most cases,
where sufficient concern exists regarding the long-term health of end organs such as the
heart, kidney, eye and brain, pharmacotherapy is recommended. Unfortunately, in these
instances drugs are prescribed with little information to guide proper, age-related dosing
or safety assessment. In studies conducted over the last decade more than half of the agents
marketed for adults with hypertension failed to demonstrate sufficient activity in children
and adolescents to meet regulatory requirements for labeling.5 While a significant amount of
this apparent ambiguity appears to be related to the design of the studies assessing the
efficacy and safety of these drugs in pediatric patients, perhaps a more significant problem
in these studies was the determination of who is actually hypertensive in the first place.
This supplement addresses this issue directly by introducing an innovative approach to the
diagnosis of hypertension in children and adolescents. Once validated, ambulatory BP
monitoring may be used to describe and model the chronobiological patterns of blood pressure
among patients who have been recently diagnosed with hypertension using standard clinical
criteria. This is a unique opportunity to assess treatment naïve patients and compare an
innovative new approach to what is currently the gold standard.
The current project is designed specifically to validate the use of ambulatory blood
pressure monitoring (ABPM) in children and adolescents so that it may be used as a clinical
tool for unambiguously making the diagnosis of hypertension in this patient population and
then be used to guide pharmacotherapeutic intervention. The use of ABPM in children was
first documented in 19916 and has subsequently been employed in children as young as 2
months of age. Despite its adjunctive use by more than 60% of pediatric nephrologists in
North America, the device currently used in the majority of pediatric practices and research
centers has never been validated in a pediatric population.
In contrast, ABPM has become a world-wide standard for monitoring blood pressure in adults
with suspected hypertension. It offers the advantages of multiple measurements of a dynamic
process over a protracted period of time and permits the evaluation of diurnal patterns and
nocturnal disease. It also offers distinct advantages in monitoring patients in their
natural environment without observer bias while permitting objective assessment of apparent
drug resistance and hypotensive events that might occur on therapy. Finally, ABPM
measurements have been demonstrated to better correlate with cardiovascular morbidity and
mortality than casual measurements.7 They also correlate with end organ damage in children.8
Performance of the proposed validation study is needed to allow for incorporation of ABPM
into clinical trial designs related to the diagnosis and treatment of hypertension in
children. ABPM will ultimately allow for more accurate determination of response to therapy
and asses the chronobiologic profile of drug response over the dosing interval. Of the
devices currently marketed, the Spacelabs 90217 offers the range of cuff sizes required by
the pediatric population. Thus, it is this monitor that will be validated.
Inclusion Criteria:
1. Age 6-18 years inclusive.
2. Mid-arm circumference measures 12-50 cm.
3. Informed consent/assent.
Exclusion Criteria:
1. Known AV fistula, unrepaired congenital heart disease, or other anatomical anomaly
affecting cardiac output and/or normal cardiac circulation.
2. Cardiac arrhythmias which may prevent the ABPM device from obtaining an accurate
blood pressure measurement.
3. Anatomical anomalies preventing measuring blood pressure in the non-dominant arm on
multiple occasions.
4. Ingestion of caffeine, tobacco exposure, or strenuous exercise within 30 minutes
before study blood pressure measurements.
5. Any condition that in the opinion of the principal investigator would affect the
subject's ability to safely and accurately complete all study procedures.
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