Losartan in Hypertensive Men and Women With Sleep Apnea Before and on Continuous Positive Airway Pressure (CPAP) Treatment

Study Overview
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Brief Summary
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Obstructive sleep apnea (OSA) is a highly prevalent condition in hypertensive patients. The renin-angiotension-aldosterone-system (RAAS) has a central role in blood pressure control. An angiotensin-II-antagonist, Losartan, is an effective antihypertensive drug. However, some patients respond to this drug worse than the others, and it is a clinical praxis to either increase the dosage and/or add another drug. There is limited data regarding the impact of antihypertensive drugs in OSA patients, i.e., whether or not OSA may constitute the subgroup of therapy-resistent hypertensive patients. In the literature, there is no data, either, whether or not CPAP treatment may have an additive blood pressure lowering impact in this certain subgroup.

Detailed Description
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OSA is a highly prevalent condition in hypertensive patients and the prevalence is even higher in patients with drug-resistant hypertension. The renin-angiotension-aldosterone-system (RAAS) has a central role in blood pressure control. An angiotensin-II-antagonist, Losartan, has an effective antihypertensive drug. However, some patients respond to this drug worse than the others, and it is a clinical praxis to either increase the dosage and/or add another drug. There is limited data regarding the impact of antihypertensive drugs in OSA patients, i.e., whether or not OSA may constitute the subgroup of therapy-resistent hypertensive patients. In the literature, there is no data, either, whether or not CPAP treatment may have an additive blood pressure lowering impact in this certain subgroup. The investigators will include 90 otherwise healthy, untreated hypertensive men and women(age 50-69 yrs, Body-Mass-Index <35 kg/m2; 60 patients with OSA, 30 non-OSA) as described above. Before start of treatment, fasting blood samples will be drawn regarding the neuroendocrine hormones (adrenaline, noradrenaline, plasma renin activity, angiotensin II,aldosterone, pro-BNP) and cardiovascular biomarkers (CRP,interleukines, cytokines). All subjects will start with Losartan 50 mg and 24 h- blood-pressure response and blood sample analysis will be compared between OSA and non-OSA subjects after 6 weeks of treatment. In the second 6-week period, all subjects will continue with Losartan while the half of the OSA group (n=30) will be randomized to CPAP and the other 30 patients will continue with Losartan only.

Official Title
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Phase 4 Study of Losartan in Hypertensive Men and Women With Obstructive Sleep Apnea Before and After Continuous Positive Airway Pressure (CPAP) Treatment

Conditions
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Hypertension, Sleep Apnea

Intervention / Treatment
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* Drug: Losartan
* Other: CPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index <35 kg/m2 Systolic Blood Pressure >=140 mmHg and/or Diastolic Blood Pressure >=95 mmHg No known clinical disease except hypertension No cardiovascular medication Apnea-Hypopnea Index < 5/h (no OSA), or Apnea Hypopnea Index >=15/h (OSA) Exclusion Criteria: Manifest diabetes, liver- or kidney disease Signs of atrial fibrillation or former myocardial infarction at electrocardiogram

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Hypertensive Men and Women Without OSA on Losartan (n=30) | Drug: Losartan<br>* Losartan 50 mg daily during 6 + 6 weeks<br>* Other names: Cozaar;|
| Active Comparator: 2<br>Hypertensive Men and Women With OSA on Losartan (n=30) | Drug: Losartan<br>* Losartan 50 mg daily during 6 + 6 weeks<br>* Other names: Cozaar;|
| Experimental: 3<br>Hypertensive Men and Women with OSA on Losartan and CPAP (n=30) | Drug: Losartan<br>* Losartan 50 mg daily during 6 + 6 weeks<br>* Other names: Cozaar;Other: CPAP<br>* CPAP during the second 6 week-period<br>* Other names: Auto-CPAP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 h blood pressure (mean blood pressure; mmHg) |  | Changes from Baseline in 24 h BP at 6 and 12 weeks, respectively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Markers of sympathetic activity, RAAS-activity, cardiovascular biomarkers |  | Changes from Baseline in Biomarkers at 6 and 12 weeks, respectively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Sleep Apnea, Angiotensin II antagonist, CPAP