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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: October 2009

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. We will include 90 otherwise healthy, untreated hypertensive men (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.

Intervention(s) in this Clinical Trial

• Drug: Losartan
  • Losartan 50 mg daily during 6 + 6 weeks
• Other: CPAP
  • CPAP during the second 6 week-period

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Hypertensive Men Without OSA on Losartan (n=30)
• Active Comparator: 2
  • Hypertensive Men With OSA on Losartan (n=30)
• Experimental: 3
  • Hypertensive Men with OSA on Losartan and CPAP (n=30)

Primary Measures

• 24 h blood pressure (mean blood pressure; mmHg)
  • Time Frame: At baseline, after 6 weeks and 12 weeks
    Safety Issue?: No

Secondary Measures

• Markers of sympathetic activity, RAAS-activity, cardiovascular biomarkers
  • Time Frame: At baseline, after 6 weeks and 12 weeks
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 69 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Skaraborg Hospital

Overall Clinical Trial Officials and Contacts

Yuksel Peker, Assoc. Prof. Principal Investigator Skaraborg Hospital, Sweden  

Overall Contact: Yuksel Peker, Assoc. Prof. +46500431000 yuksel.peker@vgregion.se

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00701428

Study ID Number: VGSKAS-12916

ClinicalTrials.gov Identifier: NCT00701428

Health Authority: Sweden: Medical Products Agency