Clinical trial NCT00701428: Losartan in Hypertensive Men and Women With Sleep Apnea Before and on Continuous Positive Airway Pressure (CPAP) Treatment
Official title: Phase 4 Study of Losartan in Hypertensive Men and Women With Obstructive Sleep Apnea Before and After Continuous Positive Airway Pressure (CPAP) Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Sleep Apnea
Keywords: Hypertension
Sleep Apnea
Angiotensin II antagonist
CPAP
Lead sponsor: Skaraborg Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Göteborg University
First posted: 2008-06-19
Enrollment: 90
Sex: ALL
Minimum age (years): 50
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 24 h blood pressure (mean blood pressure; mmHg)
timeFrame: Changes from Baseline in 24 h BP at 6 and 12 weeks, respectively
Secondary outcomes:
measure: Markers of sympathetic activity, RAAS-activity, cardiovascular biomarkers
timeFrame: Changes from Baseline in Biomarkers at 6 and 12 weeks, respectively
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: University of Gothenburg, Sahlgrenska Academy
state: West Gotaland
Study officials:
affiliation: Göteborg University
name: Yuksel Peker, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Göteborg University
name: Erik Thunström, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thunstrom E, Manhem K, Rosengren A, Peker Y. Blood Pressure Response to Losartan and Continuous Positive Airway Pressure in Hypertension and Obstructive Sleep Apnea. Am J Respir Crit Care Med. 2016 Feb 1;193(3):310-20. doi: 10.1164/rccm.201505-0998OC.
citation: Thunstrom E, Manhem K, Yucel-Lindberg T, Rosengren A, Lindberg C, Peker Y. Neuroendocrine and Inflammatory Responses to Losartan and Continuous Positive Airway Pressure in Patients with Hypertension and Obstructive Sleep Apnea. A Randomized Controlled Trial. Ann Am Thorac Soc. 2016 Nov;13(11):2002-2011. doi: 10.1513/AnnalsATS.201602-126OC.