Clinical trial NCT02896621: Effect of Antihypertensive Agents on Diastolic Function in Patients With Sleep Apnea
Official title: Effect of Antihypertensive Agents on Diastolic Function in Patients With Sleep Apnea: Protocol for a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Sleep Apnea
Keywords: Sleep Apnea
Hypertension
Chlortalidone
Diastolic function
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2016-09-12
Enrollment: 69
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators investigated diastolic function among patients with obstructive sleep apnea (OSA) and hypertension stage I. In this randomized controlled trial, participants were randomly allocated to one of two groups: chlorthalidone associated with amiloride or amlodipine. Randomization was carried out prior to the start of the trial by an epidemiologist out of clinic and the randomization list was stratified by gender and severity of OSA. The research team and participants were blinded to the randomization list and allocation concealment was implemented. This trial aimed to detect changes in the echocardiography parameters with the drug treatment (higher in the intervention than in the placebo group). The investigators also assess change in daytime sleepiness among participants who already have been diagnosed with OSA.

Detailed description: This is a randomized controlled trial, with participants randomly allocated to one of two groups: chlorthalidone associated with amiloride or amlodipine. Capsules were identical presentation and the research team and participants were blinded to the allocation list. The randomization list was stratified by gender and severity of OSA (AHI: 10-25 or 26-40) and in blocks in time, with size four and six units. Randomization was carried out prior to the start of the trial and it was generated by a validated software (Random Allocator). In order to ensure the confidentiality of the allocation list, it was generated by an epidemiologist who did not maintain direct contact with participants and the identification of the study drugs was done through alphanumeric code, implemented via software (RedCap).

Adherence to treatment was measured by counting returned capsules and through the Morisky questionnaire with eight questions, validated for Portuguese. Participants underwent initial clinical evaluation prior to randomization and after eight weeks of treatment for evaluation of outcomes. Demographic characteristics (age, gender, skin color), socioeconomic level (education), previous morbidity (diabetes mellitus, stroke, acute myocardial infarction, cancer, rheumatic diseases), treatments in use (anti-diabetic, anti-depressants, non-steroidal anti-inflammatory, corticosteroids, nasal vasoconstrictor, appetite suppressants, lipid-lowering drugs) and lifestyle characteristics (smoking and drinking) were collected in a standardized way. The investigators also assess anthropometric measures such as weight, height, waist, neck and hip circumference, and bioimpedance for determination of lean and fat mass. Blood pressure was measured using a validated digital oscillometric monitor, with cuff appropriate to the arm circumference, and two measurements per visit were made. In addition, ECG was performed and biochemical parameters (creatinine, blood glucose, serum potassium, uric acid, cholesterol and fractions, C-reactive protein and NT-proBNP) were determined in the laboratory of Hospital de Clinicas de Porto Alegre.

The transthoracic echocardiography is performed by the CX-50 unit (Philips, Bothell, WA - USA) with sectoral S5-1 transducer. Ambulatory monitoring of blood pressure will be measured through the Mortara AMBULO 2400 device (Mortara, Milwaukee, WI, USA) with measures 15/15 minutes during the day and 20/20 minutes at night, within 24 hours of a working day. Polysomnography will be held in type III (home with device that measures at least 4 cardiorespiratory variables) held with handset Sonmocheck (Weinmann GmbH, Hamburg, Germany), a monitor that detects the position of the patient, the presence of apneas or hypopneas, heart rate and digital oximetry.

Eligibility criteria: Inclusion Criteria:

* Age 40 to 70 years
* Stage I hypertension (systolic BP: 140-159 or diastolic BP: 90-99 mmHg)
* No antihypertensive treatment or use of one antihypertensive drug
* Apnea / hypopnea index: 10 to 49 AH / hour

Exclusion Criteria:

* Low life expectancy
* Indication for use of calcium channel blockers or diuretics
* Allergy medications study
* Heart failure
* Myocardial infarction
* Recent stroke (last 3 months)
* Secondary hypertension
* Participation in another clinical trial (last 6 months)
* Pregnant women

Primary outcomes:
measure: E/A ratio
timeFrame: Change at eight weeks (end of the trial)
Secondary outcomes:
measure: Daytime sleepiness
timeFrame: Change at eight weeks (end of the trial)
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RS
Study officials:
affiliation: Hospital de Clinicas de Porto Alegre
name: Sandra C Fuchs, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: