<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/NCT03839654</url>
  </required_header>
  <id_info>
    <org_study_id>2019-SR-016</org_study_id>
    <nct_id>NCT03839654</nct_id>
  </id_info>
  <brief_title>Loop Gain in the Reversion of OSA Treated by Either CPAP or Cardiac Valve Replacement</brief_title>
  <official_title>The Role and Mechanisms of Loop Gain and Associated Parameters in the Reversion of OSA Treated by Either CPAP or Cardiac Valve Replacement</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanjing Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanjing Medical 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>
      Sleep apnea including obstructive sleep apnea (OSA) and central sleep apnea (CSA), are common&#xD;
      in patients with cardiovascular disease. The prevalence of OSA is 2%-4% in general population&#xD;
      and 16%-47% in surgical-heart failure patients.&#xD;
&#xD;
      The previous studies found that the sleep apnea types shifted from OSA to CSA after&#xD;
      continuous positive airway pressure (CPAP) treatment or from CSA to OSA after heart surgery&#xD;
      (cardiac valve replacement/ repair or heart transplantation) without the mechanism&#xD;
      illuminated clearly. The recent studies found that the loop gain (LG) could predict the&#xD;
      effect of upper airway surgery and CPAP treatment on the reversion of OSA. However, in&#xD;
      patients with valvular heart disease, whether LG and related parameters can predict the&#xD;
      therapeutic efficacy of CPAP or cardiac valve replacement is not expounded clearly.&#xD;
&#xD;
      The investigators' previous study found that there were different outcomes of sleep apnea&#xD;
      after cardiac valve replacement: elimination or consistent. But the corresponding&#xD;
      non-anatomic mechanisms was not clear. The investigators' preliminary experiment showed that&#xD;
      the LG and related parameters were not improved while OSA improved by CPAP treatment;&#xD;
      however, the recovery of OSA after cardiac valve replacement was closed related to the&#xD;
      improvement of LG and related parameters.&#xD;
&#xD;
      The investigators speculated that, 1. LG and related parameters could predict OSA outcome of&#xD;
      CPAP treatment or cardiac valve replacement. 2. non-anatomic mechanisms including LG and&#xD;
      associated parameters, contributed to CPAP treatment and cardiac valve replacement were&#xD;
      different. In this study, the investigators aimed to explore the relationship between LG and,&#xD;
      outcomes of OSA and the regarding non-anatomic mechanisms in patient with heart valve&#xD;
      disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Between January 31, 2020 and June 30, 2023, 300 patients with valvular heart disease waiting&#xD;
      for cardiac valve replacement in Department of Cardiovascular Surgery were screened for&#xD;
      obstructive sleep apnea (OSA) by full-night polysomnography. Of them, 40 OSA patients were&#xD;
      enrolled and randomly received CPAP treatment and non-CPAP treatment (20:20).&#xD;
&#xD;
      The CPAP treatment group received both baseline medicine and CPAP treatment. The full-night&#xD;
      CPAP treatment was conducted from 21:00 pm to 6:00 am for 7 days preoperatively. The non-CPAP&#xD;
      treatment group received baseline medicine treatment. LG and related parameters were&#xD;
      collected at the first day of treatment in non-CPAP group and both first and last day of&#xD;
      treatment in CPAP group.&#xD;
&#xD;
      Sleep parameters including apnea-hypopnea index (AHI), mean and lowest SPO2, and clinical&#xD;
      evaluations including New York Heart Association (NYHA) classes, electrocardiographic,&#xD;
      echocardiographic, arterial blood gas analysis findings, baseline medication, and 6-minute&#xD;
      walk test were recorded.&#xD;
&#xD;
      Operation related parameters (duration of operation, duration of cardiopulmonary bypass and&#xD;
      bleeding volume) were recorded. Postoperative adverse events such as duration of ICU stay,&#xD;
      postoperative duration of mechanical ventilation, pacemaker use, complicated infection and&#xD;
      reintubations were recorded.&#xD;
&#xD;
      A full-night polysomnography as well as LG and related parameters were re-examined before&#xD;
      discharge from hospital. The changes of AHIs, mean and lowest SPO2, LG and related parameters&#xD;
      between pre- and post-operative polysomnography parameters were calculated.&#xD;
&#xD;
      The correlation between changes of polysomnography and LG parameters pre- and post-CPAP in&#xD;
      CPAP group were analyzed. The correlation between changes of polysomnography and LG&#xD;
      parameters pre- and post-operative in both CPAP and non-CPAP group were analyzed. The&#xD;
      differences of polysomnography and LG parameters, and post-operative adverse events between&#xD;
      CPAP and non-CPAP treatment group were analyzed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 31, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>A total of 300 patients with rheumatic valvular heart disease waiting for cardiac valve replacement were screened for obstructive sleep apnea (OSA). Of them, 40 OSA patients were enrolled and randomly received CPAP treatment and non-CPAP treatment (20:20 patients). The CPAP treatment group received both baseline medicine and CPAP treatment for 7 days preoperatively. The non-CPAP treatment group only received baseline medicine treatment.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>changes of apnea-hypopnea index</measure>
    <time_frame>14 days</time_frame>
    <description>Changes of apnea-hypopnea index pre- and post-operative were compared between CPAP and non-CPAP patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>changes of lowest SPO2</measure>
    <time_frame>14 days</time_frame>
    <description>Changes of lowest SPO2 pre- and post-operative were compared between CPAP and non-CPAP patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>comparison of loop gain</measure>
    <time_frame>7 days</time_frame>
    <description>Loop gain pre- and post-operative was compared between CPAP and non-CPAP patients.&#xD;
Loop gain pre- and post-CPAP treatment were compared in CPAP group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>arousal threshold</measure>
    <time_frame>14 days</time_frame>
    <description>Arousal threshold pre- and post-operative was compared between CPAP and non-CPAP patients.&#xD;
Arousal threshold pre- and post-CPAP treatment were compared in CPAP group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>upper airway gain</measure>
    <time_frame>14 days</time_frame>
    <description>Upper airway gain pre- and post-operative was compared between CPAP and non-CPAP patients.&#xD;
Upper airway gain pre- and post-CPAP treatment were compared in CPAP group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>duration of operation</measure>
    <time_frame>12 hours</time_frame>
    <description>Duration of operation was compared between CPAP and non-CPAP patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of cardiopulmonary bypass</measure>
    <time_frame>12 hours</time_frame>
    <description>Duration of cardiopulmonary bypass was compared between CPAP and non-CPAP patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of ICU stays</measure>
    <time_frame>14 days</time_frame>
    <description>Duration of ICU stays were compared between CPAP and non-CPAP patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of mechanical ventilation</measure>
    <time_frame>14 days</time_frame>
    <description>Postoperative duration of mechanical ventilation was compared between CPAP and non-CPAP patients.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Obstructive Sleep Apnea of Adult</condition>
  <condition>Heart Valve Diseases</condition>
  <arm_group>
    <arm_group_label>continuous positive airway pressure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The CPAP treatment group received both baseline medicine and CPAP treatment for 7 days preoperatively.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-continuous positive airway pressure</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The non-CPAP treatment group received baseline medicine treatment without CPAP treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>continuous positive airway pressure</intervention_name>
    <description>The CPAP treatment group received both baseline medicine and CPAP treatment for 7 days preoperatively.</description>
    <arm_group_label>continuous positive airway pressure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients aged 18-75 years.&#xD;
&#xD;
          2. Patients with heart valve disease.&#xD;
&#xD;
          3. Patients combined with obstructive sleep apnea (apnea-hypopnea index &gt;=5/h).&#xD;
&#xD;
          4. Received cardiac valve replacement surgery.&#xD;
&#xD;
          5. The enrolled patients having received patients' informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of stroke or clinical signs of peripheral or central nervous system disorders.&#xD;
&#xD;
          2. History of chronic obstructive pulmonary disease or asthma.&#xD;
&#xD;
          3. Enrolment in another clinical study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hong Wang, Ph D</last_name>
    <role>Study Director</role>
    <affiliation>The First Affiliated Hospital with Nanjing Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hong Wang, Ph D</last_name>
    <phone>8602568306723</phone>
    <email>drhongwang@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ning Ding, Ph D</last_name>
    <email>dr.ningding@live.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>the First Affiliated Hospital of Nanjing Medical University</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hong Wang, Ph D</last_name>
      <phone>25 68306723</phone>
      <email>drhongwang@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Ding Ning, Ph D</last_name>
      <email>dr.ningding@live.cn</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Ding N, Ni BQ, Zhang XL, Zha WJ, Hutchinson SZ, Lin W, Huang M, Zhang SJ, Wang H. Elimination of central sleep apnea by cardiac valve replacement: a continuous follow-up study in patients with rheumatic valvular heart disease. Sleep Med. 2014 Aug;15(8):880-6. doi: 10.1016/j.sleep.2014.02.007. Epub 2014 May 17.</citation>
    <PMID>24938583</PMID>
  </reference>
  <reference>
    <citation>Ding N, Ni BQ, Wang H, Ding WX, Xue R, Lin W, Kai Z, Zhang SJ, Zhang XL. Obstructive Sleep Apnea Increases the Perioperative Risk of Cardiac Valve Replacement Surgery: A Prospective Single-Center Study. J Clin Sleep Med. 2016 Oct 15;12(10):1331-1337. doi: 10.5664/jcsm.6182.</citation>
    <PMID>27448416</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>March 8, 2021</last_update_submitted>
  <last_update_submitted_qc>March 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nanjing Medical University</investigator_affiliation>
    <investigator_full_name>Ning Ding</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Obstructive Sleep Apnea</keyword>
  <keyword>heart valve replacement</keyword>
  <keyword>CPAP treatment</keyword>
  <keyword>loop gain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT03839654
org study id: 2019-SR-016
nct id: NCT03839654
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Sleep apnea including obstructive sleep apnea (OSA) and central sleep apnea (CSA), are common
      in patients with cardiovascular disease. The prevalence of OSA is 2%-4% in general population
      and 16%-47% in surgical-heart failure patients.

      The previous studies found that the sleep apnea types shifted from OSA to CSA after
      continuous positive airway pressure (CPAP) treatment or from CSA to OSA after heart surgery
      (cardiac valve replacement/ repair or heart transplantation) without the mechanism
      illuminated clearly. The recent studies found that the loop gain (LG) could predict the
      effect of upper airway surgery and CPAP treatment on the reversion of OSA. However, in
      patients with valvular heart disease, whether LG and related parameters can predict the
      therapeutic efficacy of CPAP or cardiac valve replacement is not expounded clearly.

      The investigators' previous study found that there were different outcomes of sleep apnea
      after cardiac valve replacement: elimination or consistent. But the corresponding
      non-anatomic mechanisms was not clear. The investigators' preliminary experiment showed that
      the LG and related parameters were not improved while OSA improved by CPAP treatment;
      however, the recovery of OSA after cardiac valve replacement was closed related to the
      improvement of LG and related parameters.

      The investigators speculated that, 1. LG and related parameters could predict OSA outcome of
      CPAP treatment or cardiac valve replacement. 2. non-anatomic mechanisms including LG and
      associated parameters, contributed to CPAP treatment and cardiac valve replacement were
      different. In this study, the investigators aimed to explore the relationship between LG and,
      outcomes of OSA and the regarding non-anatomic mechanisms in patient with heart valve
      disease.
Between January 31, 2020 and June 30, 2023, 300 patients with valvular heart disease waiting
      for cardiac valve replacement in Department of Cardiovascular Surgery were screened for
      obstructive sleep apnea (OSA) by full-night polysomnography. Of them, 40 OSA patients were
      enrolled and randomly received CPAP treatment and non-CPAP treatment (20:20).

      The CPAP treatment group received both baseline medicine and CPAP treatment. The full-night
      CPAP treatment was conducted from 21:00 pm to 6:00 am for 7 days preoperatively. The non-CPAP
      treatment group received baseline medicine treatment. LG and related parameters were
      collected at the first day of treatment in non-CPAP group and both first and last day of
      treatment in CPAP group.

      Sleep parameters including apnea-hypopnea index (AHI), mean and lowest SPO2, and clinical
      evaluations including New York Heart Association (NYHA) classes, electrocardiographic,
      echocardiographic, arterial blood gas analysis findings, baseline medication, and 6-minute
      walk test were recorded.

      Operation related parameters (duration of operation, duration of cardiopulmonary bypass and
      bleeding volume) were recorded. Postoperative adverse events such as duration of ICU stay,
      postoperative duration of mechanical ventilation, pacemaker use, complicated infection and
      reintubations were recorded.

      A full-night polysomnography as well as LG and related parameters were re-examined before
      discharge from hospital. The changes of AHIs, mean and lowest SPO2, LG and related parameters
      between pre- and post-operative polysomnography parameters were calculated.

      The correlation between changes of polysomnography and LG parameters pre- and post-CPAP in
      CPAP group were analyzed. The correlation between changes of polysomnography and LG
      parameters pre- and post-operative in both CPAP and non-CPAP group were analyzed. The
      differences of polysomnography and LG parameters, and post-operative adverse events between
      CPAP and non-CPAP treatment group were analyzed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A total of 300 patients with rheumatic valvular heart disease waiting for cardiac valve replacement were screened for obstructive sleep apnea (OSA). Of them, 40 OSA patients were enrolled and randomly received CPAP treatment and non-CPAP treatment (20:20 patients). The CPAP treatment group received both baseline medicine and CPAP treatment for 7 days preoperatively. The non-CPAP treatment group only received baseline medicine treatment.
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: changes of apnea-hypopnea index
time frame: 14 days
description: Changes of apnea-hypopnea index pre- and post-operative were compared between CPAP and non-CPAP patients.
measure: changes of lowest SPO2
time frame: 14 days
description: Changes of lowest SPO2 pre- and post-operative were compared between CPAP and non-CPAP patients.
measure: comparison of loop gain
time frame: 7 days
description: Loop gain pre- and post-operative was compared between CPAP and non-CPAP patients.
Loop gain pre- and post-CPAP treatment were compared in CPAP group.
measure: arousal threshold
time frame: 14 days
description: Arousal threshold pre- and post-operative was compared between CPAP and non-CPAP patients.
Arousal threshold pre- and post-CPAP treatment were compared in CPAP group.
measure: upper airway gain
time frame: 14 days
description: Upper airway gain pre- and post-operative was compared between CPAP and non-CPAP patients.
Upper airway gain pre- and post-CPAP treatment were compared in CPAP group.
measure: duration of operation
time frame: 12 hours
description: Duration of operation was compared between CPAP and non-CPAP patients.
measure: duration of cardiopulmonary bypass
time frame: 12 hours
description: Duration of cardiopulmonary bypass was compared between CPAP and non-CPAP patients.
measure: duration of ICU stays
time frame: 14 days
description: Duration of ICU stays were compared between CPAP and non-CPAP patients.
measure: duration of mechanical ventilation
time frame: 14 days
description: Postoperative duration of mechanical ventilation was compared between CPAP and non-CPAP patients.
arm group label: continuous positive airway pressure
arm group type: Experimental
description: The CPAP treatment group received both baseline medicine and CPAP treatment for 7 days preoperatively.
arm group label: non-continuous positive airway pressure
arm group type: No Intervention
description: The non-CPAP treatment group received baseline medicine treatment without CPAP treatment.
intervention type: Device
intervention name: continuous positive airway pressure
description: The CPAP treatment group received both baseline medicine and CPAP treatment for 7 days preoperatively.
arm group label: continuous positive airway pressure
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hong Wang, Ph D
role: Study Director
affiliation: The First Affiliated Hospital with Nanjing Medical University
last name: Hong Wang, Ph D
phone: 8602568306723
email: drhongwang@163.com
last name: Ning Ding, Ph D
email: dr.ningding@live.cn
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
citation: Ding N, Ni BQ, Zhang XL, Zha WJ, Hutchinson SZ, Lin W, Huang M, Zhang SJ, Wang H. Elimination of central sleep apnea by cardiac valve replacement: a continuous follow-up study in patients with rheumatic valvular heart disease. Sleep Med. 2014 Aug;15(8):880-6. doi: 10.1016/j.sleep.2014.02.007. Epub 2014 May 17.
PMID: 24938583
citation: Ding N, Ni BQ, Wang H, Ding WX, Xue R, Lin W, Kai Z, Zhang SJ, Zhang XL. Obstructive Sleep Apnea Increases the Perioperative Risk of Cardiac Valve Replacement Surgery: A Prospective Single-Center Study. J Clin Sleep Med. 2016 Oct 15;12(10):1331-1337. doi: 10.5664/jcsm.6182.
PMID: 27448416
responsible party type: Principal Investigator
investigator affiliation: Nanjing Medical University
investigator full name: Ning Ding
investigator title: Principal Investigator
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Heart Valve Diseases