Nocturnal Oxygen Needs and Central Sleep Apnea in Patients With Chronic Heart Failure. (HO2F)

• ClinicalTrials.gov Identifier: NCT03254212
• Recruitment Status: Recruiting
• First Posted: August 18, 2017
• Last Update Posted: February 21, 2020
• Sponsor: Laval University
• Collaborators: Oxynov; Philips Respironics
• Information provided by (Responsible Party): Frédéric Sériès, Laval University

Study Description

Brief Summary:

The aims of this study are to 1) determine the optimal levels of O2 flow which prevent nocturnal O2 desaturation while minimizing periods of hyperoxia during the course of nocturnal oxygen therapy (NOXT) in heart failure patients with reduced ejection fraction (HFrEF) patients with CSA/CSR; 2) document whether within-patient EO2F values change over time during NOXT, and identify factors which predict changes in EO2F; and 3) examine how well a conventional stepwise titration procedure compares to a breath by breath titration using an automated O2 titration system in terms of targeted flow rate and night time oxygenation (oxygen desaturation index, time spent at specific SpO2 targets).

Condition or disease	Intervention/treatment	Phase
Chronic Heart Failure; Central Sleep Apnea	Device: Titration of nocturnal oxygen needs to prevent desaturations	Phase 4

Detailed Description:

Sleep-related breathing disorders (obstructive and central) are highly prevalent in Heart failure (HF) patients and are associated with an increase in morbidity and mortality. Nocturnal oxygen therapy (NOT) reduces the frequency of central breathing events by 75 % and prevents nocturnal desaturation in patients with HF. Considering that the amount of nocturnal desaturation is a better predictor of mortality than the apnea+hypopnea index (AHI) in this population, one should expect NOT to have a positive impact on survival in these patients. In the four randomized clinical trials where the effects of O2 on left ventricular function was assessed, 2 reported a significant increase in LVEF after 3 months of NOT. NOT was also found to positively impact on other important predictive factors of mortality such as sympathetic activity and VO2 max. These mitigated results could be accounted by the fact that a fixed O2 flow was empirically used (2 to 4 L/min) in the majority of studies. This may impede the beneficial effects of NOT for two reasons. First, in patients with HF, oxygen is associated with a dose-related detrimental hemodynamic effects (i.e. increase in vascular resistance and reduction in cardiac output and stroke volume). Therefore, the lowest O2 flow that prevents nocturnal desaturation should be used to minimize the detrimental effects of hyperoxia. On the other hand, there are evidences that the frequency and/or severity of sleep-disordered breathing may change overtime in CHF patients leading to insufficient correction of nocturnal desaturation during the course of NOT. Therefore, NOT should be preceded by an oxygen titration procedure to determine the lowest O2 flow that prevents nocturnal desaturation. This can be done with a stepwise night-to-night increase in O2 flow until correction of nocturnal desaturation. However, another approach would be to prevent event-by-event desaturations and to prevent hyperoxia during periods of normal sleep and wakefulness. On the other hand, the stability in O2 needs overtime in these patients is unkown. The aims of this study are 1) to document if the level of O2 flow preventing nocturnal desaturation changes during the course of NOT in CHF patients with CSA/CSR and 2) to examine the ability of automated O2 titration (FreeO2, Oxynov, Quebec, Canada) to determine O2 needs in HF patients with CSA/CSR when compared to the gold standard titration procedure.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 14 participants
• Intervention Model: Sequential Assignment
• Intervention Model Description: Fixed nightime oxygen therapy throughout the study duration with oxygen flow determined according to the results of the home oxygen titration procedure.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Nocturnal Oxygen Needs in the Treatment of Central Sleep Apnea in Patients With Chronic Heart Failure.
• Actual Study Start Date: April 15, 2018
• Estimated Primary Completion Date: October 30, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Oxygen therapy; Fixed nightime oxygen therapy throughout the protocol duration

Device: Titration of nocturnal oxygen needs to prevent desaturations; Oximetry recordings will be performed using a Pulse Oximeter. Two O2 titration sessions will be conducted at home in random order one week apart. One will consist of a stepwise night-to-night increase in O2 flow for up to 4 nights with supplemental O2, each at flow rates of 1L/min, 2L/min, 3L/min and 4L/min, respectively. During the other titration session, an automatic O2 delivery system will be used for 4 consecutive nights with O2 flow allowed to vary from 0 to 4 L/min with a 95 ± 2% SpO2 target. At the end of the titration periods, oxygen concentrators will be set at the lowest flow rate (1L/min to 4L/min) that maintained oxyhemoglobin saturation to > 90% (Tsat90%) for ≥ 98% of the estimated sleep period and reduced the oxygen desaturation index 3% (ODI3) to < 5/hour according to conventional O2 titration. If these targets are not reached, the lowest flow rate will be selected that minimizes the ODI3. These procedures will be repeated at week 5 and 11.

Outcome Measures

Primary Outcome Measures :

1. Changes in optimal levels of O2 flow ( EO2F) which prevent nocturnal O2 desaturation [ Time Frame: Three months ( titration completed 3 times during the study period) ]
   changes in the lowest flow rate (1L/min to 4L/min) that maintained oxyhemoglobin saturation to > 90% (Tsat90%) for ≥ 98% of the estimated sleep period and reduced the oxygen desaturation index (ODI3P) to < 5/hour
2. Accuracy of automated oxygen titration [ Time Frame: Three months (new titration sessions completed 3 times during the study period) ]
   examine how well a conventional stepwise titration procedure compares to a breath by breath titration using an automated O2 titration system in terms of targeted flow rate and night time oxygenation (oxygen desaturation index, time spent at specific SpO2 targets)

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• patients with heart failure and reduced ejection fraction (LVEF < 45%) due to ischemic or hypertensive heart disease
• moderate to severe central sleep apnea/cheyne stokes respiration.
• treatment should be stable for the last 30 days preceding entry into the study.

Exclusion Criteria:

• O2 /CPAP therapy,
• active smoking,
• primary valvular heart disease,
• nasal obstruction,
• BMI ≥ 32 Kg/m2,
• cardiac surgery/transient ischemic attack/stroke/resynchronization therapy within 3 months,
• nocturnal hypoventilation,
• receiving opiates or methadone medication.

Contacts and Locations

Contacts

Contact: Frederic Series, MD; 418 656 8711 ext 5513; frederic.series@med.ulaval.ca

Contact: Hugo Tremblay, MSc; 418 656 8711 ext 3797; hugo.tremblay@criucpq.ulaval.ca

Locations

Canada, Qiebec

Frédéric Sériès; Recruiting

Quebec city, Qiebec, Canada, G1V 4G5

Contact: Frédéric Sériès, MD 418 656 4747 frederic.series@med.ulaval.ca

Contact: Frédéric Sériès, MD 418 656 4747 ftrederic.series@med.ulaval.ca

Canada, Quebec

John Kimoff; Recruiting

Montréal, Quebec, Canada, H4A 3J1

Contact: John Kimoff, MD 514-934-1934 john.kimoff@mcgill.ca

Sponsors and Collaborators

Laval University

Oxynov

Philips Respironics

More Information

• Responsible Party: Frédéric Sériès, Director IUCPQ Sleep laboratory, Laval University
• ClinicalTrials.gov Identifier: NCT03254212
• Other Study ID Numbers: OXY-GRA-17027-LOFTHF-SH
• First Posted: August 18, 2017
• Last Update Posted: February 21, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Frédéric Sériès, Laval University:

Heart failure; Central sleep apnea; oxygen therapy

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Central; Heart Failure; Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases