<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03254212</url>
  </required_header>
  <id_info>
    <org_study_id>OXY-GRA-17027-LOFTHF-SH</org_study_id>
    <nct_id>NCT03254212</nct_id>
  </id_info>
  <brief_title>Nocturnal Oxygen Needs and Central Sleep Apnea in Patients With Chronic Heart Failure.</brief_title>
  <acronym>HO2F</acronym>
  <official_title>Evaluation of Nocturnal Oxygen Needs in the Treatment of Central Sleep Apnea in Patients With Chronic Heart Failure.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laval University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oxynov</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Philips Respironics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Laval University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aims of this study are to 1) determine the optimal levels of O2 flow which prevent&#xD;
      nocturnal O2 desaturation while minimizing periods of hyperoxia during the course of&#xD;
      nocturnal oxygen therapy (NOXT) in heart failure patients with reduced ejection fraction&#xD;
      (HFrEF) patients with CSA/CSR; 2) document whether within-patient EO2F values change over&#xD;
      time during NOXT, and identify factors which predict changes in EO2F; and 3) examine how well&#xD;
      a conventional stepwise titration procedure compares to a breath by breath titration using an&#xD;
      automated O2 titration system in terms of targeted flow rate and night time oxygenation&#xD;
      (oxygen desaturation index, time spent at specific SpO2 targets).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sleep-related breathing disorders (obstructive and central) are highly prevalent in Heart&#xD;
      failure (HF) patients and are associated with an increase in morbidity and mortality.&#xD;
      Nocturnal oxygen therapy (NOT) reduces the frequency of central breathing events by 75 % and&#xD;
      prevents nocturnal desaturation in patients with HF. Considering that the amount of nocturnal&#xD;
      desaturation is a better predictor of mortality than the apnea+hypopnea index (AHI) in this&#xD;
      population, one should expect NOT to have a positive impact on survival in these patients. In&#xD;
      the four randomized clinical trials where the effects of O2 on left ventricular function was&#xD;
      assessed, 2 reported a significant increase in LVEF after 3 months of NOT. NOT was also found&#xD;
      to positively impact on other important predictive factors of mortality such as sympathetic&#xD;
      activity and VO2 max. These mitigated results could be accounted by the fact that a fixed O2&#xD;
      flow was empirically used (2 to 4 L/min) in the majority of studies. This may impede the&#xD;
      beneficial effects of NOT for two reasons. First, in patients with HF, oxygen is associated&#xD;
      with a dose-related detrimental hemodynamic effects (i.e. increase in vascular resistance and&#xD;
      reduction in cardiac output and stroke volume). Therefore, the lowest O2 flow that prevents&#xD;
      nocturnal desaturation should be used to minimize the detrimental effects of hyperoxia. On&#xD;
      the other hand, there are evidences that the frequency and/or severity of sleep-disordered&#xD;
      breathing may change overtime in CHF patients leading to insufficient correction of nocturnal&#xD;
      desaturation during the course of NOT. Therefore, NOT should be preceded by an oxygen&#xD;
      titration procedure to determine the lowest O2 flow that prevents nocturnal desaturation.&#xD;
      This can be done with a stepwise night-to-night increase in O2 flow until correction of&#xD;
      nocturnal desaturation. However, another approach would be to prevent event-by-event&#xD;
      desaturations and to prevent hyperoxia during periods of normal sleep and wakefulness. On the&#xD;
      other hand, the stability in O2 needs overtime in these patients is unkown. The aims of this&#xD;
      study are 1) to document if the level of O2 flow preventing nocturnal desaturation changes&#xD;
      during the course of NOT in CHF patients with CSA/CSR and 2) to examine the ability of&#xD;
      automated O2 titration (FreeO2, Oxynov, Quebec, Canada) to determine O2 needs in HF patients&#xD;
      with CSA/CSR when compared to the gold standard titration procedure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 15, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in optimal levels of O2 flow ( EO2F) which prevent nocturnal O2 desaturation</measure>
    <time_frame>Three months ( titration completed 3 times during the study period)</time_frame>
    <description>changes in the lowest flow rate (1L/min to 4L/min) that maintained oxyhemoglobin saturation to &gt; 90% (Tsat90%) for ≥ 98% of the estimated sleep period and reduced the oxygen desaturation index (ODI3P) to &lt; 5/hour</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Accuracy of automated oxygen titration</measure>
    <time_frame>Three months (new titration sessions completed 3 times during the study period)</time_frame>
    <description>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)</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">14</enrollment>
  <condition>Chronic Heart Failure</condition>
  <condition>Central Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>Oxygen therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fixed nightime oxygen therapy throughout the protocol duration</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Titration of nocturnal oxygen needs to prevent desaturations</intervention_name>
    <description>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 &gt; 90% (Tsat90%) for ≥ 98% of the estimated sleep period and reduced the oxygen desaturation index 3% (ODI3) to &lt; 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.</description>
    <arm_group_label>Oxygen therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with heart failure and reduced ejection fraction (LVEF &lt; 45%) due to ischemic&#xD;
             or hypertensive heart disease&#xD;
&#xD;
          -  moderate to severe central sleep apnea/cheyne stokes respiration.&#xD;
&#xD;
          -  treatment should be stable for the last 30 days preceding entry into the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  O2 /CPAP therapy,&#xD;
&#xD;
          -  active smoking,&#xD;
&#xD;
          -  primary valvular heart disease,&#xD;
&#xD;
          -  nasal obstruction,&#xD;
&#xD;
          -  BMI ≥ 32 Kg/m2,&#xD;
&#xD;
          -  cardiac surgery/transient ischemic attack/stroke/resynchronization therapy within 3&#xD;
             months,&#xD;
&#xD;
          -  nocturnal hypoventilation,&#xD;
&#xD;
          -  receiving opiates or methadone medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Frederic Series, MD</last_name>
    <phone>418 656 8711</phone>
    <phone_ext>5513</phone_ext>
    <email>frederic.series@med.ulaval.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hugo Tremblay, MSc</last_name>
    <phone>418 656 8711</phone>
    <phone_ext>3797</phone_ext>
    <email>hugo.tremblay@criucpq.ulaval.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Frédéric Sériès</name>
      <address>
        <city>Quebec city</city>
        <state>Qiebec</state>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frédéric Sériès, MD</last_name>
      <phone>418 656 4747</phone>
      <email>frederic.series@med.ulaval.ca</email>
    </contact>
    <contact_backup>
      <last_name>Frédéric Sériès, MD</last_name>
      <phone>418 656 4747</phone>
      <email>ftrederic.series@med.ulaval.ca</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>John Kimoff</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John Kimoff, MD</last_name>
      <phone>514-934-1934</phone>
      <email>john.kimoff@mcgill.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>April 6, 2022</last_update_submitted>
  <last_update_submitted_qc>April 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Laval University</investigator_affiliation>
    <investigator_full_name>Frédéric Sériès</investigator_full_name>
    <investigator_title>Director IUCPQ Sleep laboratory</investigator_title>
  </responsible_party>
  <keyword>Heart failure</keyword>
  <keyword>Central sleep apnea</keyword>
  <keyword>oxygen therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Central</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03254212
org study id: OXY-GRA-17027-LOFTHF-SH
nct id: NCT03254212
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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).
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.
allocation: N/A
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.
primary purpose: Treatment
masking: None (Open Label)
measure: 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)
description: 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
measure: Accuracy of automated oxygen titration
time frame: Three months (new titration sessions completed 3 times during the study period)
description: 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)
arm group label: Oxygen therapy
arm group type: Experimental
description: Fixed nightime oxygen therapy throughout the protocol duration
intervention type: Device
intervention name: Titration of nocturnal oxygen needs to prevent desaturations
description: 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.
arm group label: Oxygen therapy
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Frederic Series, MD
phone: 418 656 8711
phone ext: 5513
email: frederic.series@med.ulaval.ca
last name: Hugo Tremblay, MSc
phone: 418 656 8711
phone ext: 3797
email: hugo.tremblay@criucpq.ulaval.ca
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Laval University
investigator full name: Frédéric Sériès
investigator title: Director IUCPQ Sleep laboratory
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Central
mesh term: Heart Failure
sharing ipd: No