Impact of Obstructive Sleep Apnea (OSA) Treatment on Blood Pressure Control in Chronic Kidney Disease

Impact of Obstructive Sleep Apnea Treatment on Blood Pressure Control in Chronic Kidney Disease: A Randomized Trial

The role of obstructive sleep apnea (OSA) on chronic kidney disease (CKD) is not clear. This randomized clinical trial will test the impact of OSA treatment on blood pressure (BP) and on the estimated glomerular filtration rate (eGFR) in patients with CKD IIIb and IV (eGFR 44-15 ml/min). A polygraph will be performed to assess the presence of OSA (defined by an apnea-hypopnea index ≥15 events/hour). Patients with OSA will be randomized to use continuous positive upper airway pressure (CPAP) or to maintain optimized clinical treatment for BP control. Antihypertensive medication adjustments will be allowed using a standard protocol for both groups by the same researcher, who will not have access to CPAP follow-up. In addition to clinical (including BP and ambulatory BP monitoring, ABPM) and laboratory assessments at baseline, we will follow up at 3 months, 6 months, 9 months and 12 months after randomization of the proposed outcomes. Target organ damage analyses, such as the retina and echocardiography, will be performed at baseline and after 1 year of randomization. Primary objective: to compare the effect of CPAP on the need to adjust antihypertensive medication to control systolic BP (<130mmHg) in patients with CKD; secondary objectives: 1) to evaluate the reduction in systolic and diastolic BP by office and ABPM; 2) assessment of nocturnal BP dipping; 3) to evaluate the impact of OSA treatment with CPAP on eGFR during follow-up; 4) to evaluate the impact of OSA treatment with CPAP on the evolution of albuminuria; 5) assessment of other target organ damage such as retinopathy and cardiac remodeling; 6) to evaluate the impact of OSA treatment with CPAP on the possible delay for renal replacement therapy or end-stage renal disease (eGFR <15ml/min and dialysis); 7) to evaluate the impact of OSA treatment with CPAP on the quality of life of patients with CKD. With a significance level of 5% and study power of 90%, two-tailed hypothesis testing, 74 patients with OSA per group, i.e., 148 patients in total, will be required to assess the primary endpoint (we estimate that 25% and 50% of patients in control and CPAP groups will not need to adjust their antihypertensive medication at follow-up, respectively).

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Sleep Apnea
• Intervention / Treatment: Device: CPAP; Drug: Usual care

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Luciano Drager, MD, PhD; Phone Number: 5511-26617686; Email: luciano.drager@incor.usp.br
• Study Contact Backup: Name: Fernanda Trani Ferreira, MD; Phone Number: 5511-26617686; Email: tranifernanda@gmail.com

Study Locations

• Brazil
  • São Paulo, Brazil
    • Recruiting
    • Fernanda Trani Ferreira
    • Contact: Fernanda Trani Ferreira, MD; Phone Number: 5511-26617686; Email: tranifernanda@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of hypertension: Use of oral antihypertensive drugs or systolic BP (SBP) >140 mmHg and/or diastolic BP (DBP) >90 mmHg on 2 office measurements or >130x80 mmHg (24 hours ABPM).
• eGFR by the CKD-EPI equation between 45 ml/min/1.73m2 and 15 ml/min/1.73m2 (in conservative treatment of CKD).

Exclusion Criteria:

• Professional drivers;
• Home supplemental oxygen users;
• Patients under current treatment for OSA;
• Pregnant women;
• Patients with malignant neoplasms or terminal illnesses;
• Severe asthma or chronic obstructive pulmonary disease;
• Patients with systemic lupus erythematosus, amyloidosis or systemic sclerosis;
• Patients with a history of solid organ transplants.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous positive airway pressure (CPAP); Standard OSA treatment + BP adjustments with anti-hypertensive therapy	Device: CPAP; Continuous positive airway pressure + anti-hypertensive treatment intensification (if necessary)
Active Comparator: Usual Care; BP adjustments with anti-hypertensive therapy	Drug: Usual care; Anti-hypertensive treatment intensification (if necessary)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-hypertensive intensification	Percentage of patients that required treatment modification aiming at blood pressure control	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic and diastolic blood pressure change by office measurement and ambulatory blood pressure monitoring	Absolute blood pressure change	1 year
Nocturnal blood pressure dipping	Assessment of nocturnal blood pressure dipping using ambulatory blood pressure monitoring	1 year
Estimated glomerular filtration rate (eGFR)	Impact of OSA treatment with CPAP on eGFR	1 year
Albuminuria	Impact of OSA treatment with CPAP on the evolution of albuminuria	1 year
Target organ damage using echocardiogram and fundoscopy	Impact of OSA treatment with CPAP on target organ damage such as grade of retinopathy and cardiac remodeling (left ventricular mass index, diastolic dysfunction, etc. by echocardiography).	1 year
End-stage renal disease (need of dialysis)	Impact of OSA treatment with CPAP on the possible delay for renal replacement therapy or end-stage renal disease (eGFR <15ml/min)	1 year
Continuous analysis of Quality of life	Impact of OSA treatment with CPAP on the quality of life (measured by 36-Item Short Form Health Survey). The lowest and highest possible scores are 0 and 100, respectively. The lower the score the higher impairment in quality of life.	1 year

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Investigators: Principal Investigator: Luciano Drager, MD, PhD, University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: April 14, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Urologic Diseases; Disease Attributes; Renal Insufficiency; Signs and Symptoms, Respiratory; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Kidney Diseases; Renal Insufficiency, Chronic; Apnea
• Other Study ID Numbers: 64401922.8.0000.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No