Treatment of OSA Associated Hypertension With Nebivolol or Hydrochlorothiazide (nebhctz)
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|ClinicalTrials.gov Identifier: NCT02710071|
Recruitment Status : Completed
First Posted : March 16, 2016
Last Update Posted : May 23, 2016
|Condition or disease||Intervention/treatment||Phase|
|Hypertension||Drug: Nebivolol Drug: Hydrochlorothiazide||Phase 4|
This is a blinded crossover study measuring the antihypertensive efficacy of nebivolol vs HCTZ in up to 34 subjects. Subjects with an apnea-hypopnea index (AHI) > 10 and hypertension can enter the study. Hypertension is defined as a systolic blood pressure (SBP) > 140 or a diastolic blood pressure (DBP) > 90 on the average of three seated blood pressure measurements or a history of medical therapy for hypertension. Subjects who have tried and abandoned continuous positive airway pressure (CPAP) therapy for sleep apnea are eligible for this study. All others will be advised that CPAP is preferred treatment for sleep apnea and are eligible only if they decline CPAP or use it for too short a time at night to be effective.
Then patients will have their antihypertensive drugs tapered off and receive single blind placebo for two weeks. After that, all subjects receive nebivolol or HCTZ for six weeks with a full evaluation at that time. Subjects are crossed over to HCTZ 12.5 mg for 2 weeks followed by HCTZ 25 mg for 4 more weeks. Nebivolol 5 mg will be taken daily at bedtime for 2 weeks and then as a dose of 10 mg for the remaining 4 weeks. Subjects will receive a telephone call at the time of increased dosage as a reminder. Blood, urine and 24-hour blood pressure measurements, hemodynamic measurements, questionnaires and drug accountability are measured in the same manner toward at the the end of placebo and each drug treatment. The entire study will take 14 weeks, although each study period may be lengthened by one week if necessary for the convenience of the subject's personal schedule.
Patients will provide blood pressure readings from their home monitor or in clinic and will not have the dose increased if they have systolic blood pressure below 105 mm Hg or side effects suggesting that an increased dose might worsen side effects
At the end of each treatment period, subjects will undergo noninvasive hemodynamic testing. Ultrasound will be used to measure aortic diameter and blood velocity in the ascending aorta in order to better estimate cardiac output. Then, finger plethysmography will be used to acquire beat-to-beat finger blood pressure and pulse rate. Beat-to-beat derived hemodynamic variables will be calculated by a model flow algorithm (e.g. brachial artery flow, stroke volume, cardiac output, ejection time, blood pressure rate of change, peripheral resistance). Applanation tonometry will be used to obtain pulse wave velocity and central arterial pressure. ECG will be recorded with standard ECG leads to determine heart rate variability in both time and frequency domains. Spontaneous baroreflex will be determined from beat-to-beat changes in blood pressure and pulse pressure interval. Forearm reactive hyperemia will be used to quantify endothelial dysfunction during 4 minutes of post-ischemic change. Subjects will then complete an Epworth Sleepiness Scale questionnaire (ESS) and a Functional Outcomes of Sleep Questionnaire (FOSQ) to find whether they are drowsy in the daytime and if they feel that they are compromised by not having adequate rest. Any adverse event will be recorded. They are asked about any concurrent medication over the prior period, including prescription medication, over the counter medication, and caffeine intake. Medication compliance is evaluated by pill count. Those who fail to return their pill bottle are requested to bring it in. Finally, a 24-hour ambulatory blood pressure monitor (ABPM) will be attached to automatically collect blood pressure and heart rate values every 15 minutes during the wake period and every 30 minutes during the sleep period.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||A Blinded Crossover Study of the 24 Hour Blood Pressure Response to Treatment of Obstructive Sleep Apnea Associated Hypertension With Nebivolol or Hydrochlorothiazide|
|Study Start Date :||January 2015|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||April 2016|
Active Comparator: Nebivolol 5mg for 2 weeks then 10 mg
Nebivolol 5 mg for 2 weeks followed by nebivolol 10 mg for 4 weeks
Nebivolol 5mg then nebivolol 10 mg
Other Name: Bystolic
Active Comparator: HCTZ 12.5 mg for 2 weeks then 25 mg
Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks
Hydrochlorothiazide 12.5 mg then hydrochlorothiazide 25 mg
Other Name: Hydrodiuril
- 24 hour diastolic blood pressure [ Time Frame: 6 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02710071
|Principal Investigator:||Michael G. Ziegler, M.D.||Professor of Medicine|