Clinical trial NCT01070342: Ambulatory Blood Pressure Monitoring in Children
Official title: Methodological Improvement in Measuring Efficacy Outcome in Antihypertensive Trials in Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Blood Pressure
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: University of California, San Diego
name: Arkansas Children's Hospital Research Institute
name: University of Cincinnati
name: University of Louisville
First posted: 2010-02-18
Enrollment: 170
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children ages 6 to 18 years will be available for participation in this multicenter study. Subjects will be enrolled from community based general pediatric clinics and other well-child care areas within participating hospitals and clinics of the four participating sites. Enrollment will continue until a total of 85 subjects from each age category (6-\<12 years and ≥12- \<18 years) successfully complete the study. In addition, enrollment will be dependent upon mean qualifying blood pressure and arm circumference such that a wide range of both are represented in each age group.

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To validate the Ambulatory Blood Pressure Monitoring device most commonly used in children (Spacelabs 90217 - Issaquah, Washington) has not been independently validated for use in this population.
timeFrame: 30 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital Research Institute
state: Arkansas
city: Louisville
country: United States
facility: University of Louisville Research Foundation, Inc.
state: Kentucky
Study officials:
affiliation: Universtiy Hosptials Case Medical Center
name: Jeffrey L. Blumer, Ph.D., M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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