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Morphine in Moderate Obstructive Sleep Apnoea (MIMOSA)

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ClinicalTrials.gov Identifier: NCT03127800
Recruitment Status : Terminated (Difficulties with recruitment)
First Posted : April 25, 2017
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Papworth Hospital NHS Foundation Trust

Brief Summary:

The aim of this study is to investigate the effects of morphine (a drug commonly used for the treatment of moderate to severe pain, particularly following surgery) on the number of pauses in breathing in patients with moderate obstructive sleep apnoea (OSA). Morphine has been shown to reduce upper airway muscle tone and can also cause shallow breathing, which can affect breathing function in patients with sleep apnoea. However, to date these effects have not been proven in clinical trials. Although, caution is advised when prescribing morphine to patients with sleep apnoea, there is currently no strong evidence that morphine makes sleep apnoea worse. Only one randomised controlled trial (considered the gold standard in medical research) has shown no worsening of symptoms for patients with sleep apnoea. The effect of morphine on patients with sleep apnoea will be assessed in a safe, controlled, hospital environment. Information from the study will help inform doctors about the safety of giving morphine to patients with sleep apnoea in urgent situations, for example after surgery.

The results of this study will enable clinicians to make better decisions when prescribing this drug to patients with OSA in the future.


Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnoea Drug: Morphine sulphate Phase 3

Detailed Description:

Sleep Disordered Breathing (SDB) is a term used to cover a range of breathing events encountered during sleep and includes Obstructive Sleep Apnoea (OSA). OSA is the most common form of SDB and is caused by partial or complete upper airway occlusion during sleep leading to repetitive arousals to restore the airway patency. These frequent, obstructive events can be associated with symptoms of unrefreshing sleep and adverse health outcomes. The incidence of OSA is increasing due to rising levels of obesity, which has been identified as the strongest risk factor for developing OSA. It is estimated that at present 80% of sufferers are undiagnosed. It must therefore be assumed that some of these patients are referred for surgery.

Morphine, opiates and opioids remain the treatment of choice for moderate and severe pain relief. Inevitably, a large number of patients will be presenting for surgery and receiving postoperative opioid analgesia. Opioids may reduce respiratory rate and tidal volume, decrease chemoresponsiveness to hypercapnia/hypoxia as well as decrease upper airway muscle tone. These effects might further impair respiratory function in patients with SDB. There is limited data showing increased extubation complications, increased incidence of paradoxical breathing patterns and pronounced oxygen desaturations in patients with SDB receiving opioid-based analgesia, but only one randomised controlled trial examining the effect of an opioid in subjects with SDB.

Therefore, the current evidence base regarding the management of patients with OSA and their peri-operative risk is sparse. As such the current recommendation from the American Society of Anaesthesiologists to limit the use of opioids in such patients, is based on expert opinion only. Indeed the effect of opioid analgesia on patients with SDB remains poorly understood, making informed decisions when prescribing such substances to patients with SDB a challenge.

This prospective, paired design trial will investigate the effect of intravenous morphine sulphate on respiration during sleep in patients with moderate OSA.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: The Effect of Acute Intravenous Morphine Administration on Sleep Disordered Breathing (SDB) in Patients With Moderate Obstructive Sleep Apnoea (OSA): A Paired Design Trial
Actual Study Start Date : May 20, 2016
Actual Primary Completion Date : November 4, 2017
Actual Study Completion Date : June 6, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Experimental: Morphine sulphate
Participants will be given a first dose of morphine sulphate (intravenously) before bedtime and a second dose four hours later. In both instances 4 mg of intravenous ondansetron will be administered after the morphine sulphate dose to prevent sickness
Drug: Morphine sulphate
5mg of intravenous morphine sulphate diluted to 5ml with normal saline (0.9% sodium chloride) will be administered 30 minutes before participant's bed time. The same dose will be administered four hours later. In both instances 4 mg of intravenous ondansetron will be administered after the morphine sulphate dose to prevent sickness.
Other Name: Morphine sulphate 10mg/ml




Primary Outcome Measures :
  1. Change in Apnoea-Hypopnea Index (AHI) [ Time Frame: Change in AHI from baseline Respiratory Polygraphy (rPSG) through to completion of study at overnight visit, within 4 months of baseline ]
    Change in the mean number of apnoeas and hypopneas.


Secondary Outcome Measures :
  1. Change in arterial oxygen desaturations [ Time Frame: Change in arterial oxygen desaturations from baseline Respiratory Polygraphy (rPSG) through to completion of study at overnight visit, within 4 months of baseline ]
    Number of arterial oxygen desaturations of greater than or equal to 4% per hour (Oxygen Desaturation Index) measured by pulse oximetry during the rPSG

  2. Change in the percentage of time spent with nocturnal saturations [ Time Frame: Change in percentage of time spent with nocturnal saturations from baseline Respiratory Polygraphy (rPSG) through to completion of study at overnight visit, within 4 months of baseline ]
    Percentage of time spent with nocturnal saturations of less than or equal to 90% measured by pulse oximetry during the rPSG



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Patients with diagnosis of moderate or severeOSA at screening, diagnosed by nocturnal oximetry, rPSG or PSG (defined as AHI or ODI of 15-50 events/hour) established on Continuous Positive Airway Pressure (CPAP)
  3. Patients established on CPAP with confirmed moderate OSA (AHI 15-29 events/hr) 6 nights after withdrawal of CPAP (confirmed at baseline rPSG)
  4. Patients diagnosed with moderate OSA by rPSG or PSG, naïve to CPAP treatment

Exclusion Criteria:

  • Inability to give informed consent or comply with the protocol
  • Current, clinically significant acute respiratory tract infection (at screening and at study visit)
  • Chronic respiratory disease (other than OSA), symptomatic ischemic heart disease
  • Pregnancy or suspected pregnancy/breast feeding
  • Current or recent (within last week of entering the trial and for the duration fo the trial) use of gabapentin, pregabalin, melatonin, mirtazapine, benzodiazepines, barbiturates, sodium oxybate, ramelteon, Z-drugs and opiates/opioids
  • Monoamine oxidase inhibitors (MAOIs), linezolid taken within two weeks of participation in the trial
  • A known allergy to the investigational medicinal product (IMP) or non investigational medicinal product(s) (NIMP)(s)
  • Patients with an inadequate command of English and such that an interpreter would be required overnight
  • Change in weight of greater than 5% since the baseline rPSG
  • Vital signs recordings (oxygen saturations, blood pressure, pulse rate) that in the clinician's opinion deem the patient unsafe to participate in the trial
  • Clinician deems the patient unsafe to participate in the trial (e.g. severely sleepy patients who cannot withdraw from CPAP)
  • CPAP intolerant/poor responder
  • History of drug abuse (oral and intravenous) including: alcohol, substituted amphetamines, barbiturates, benzodiazepines, cocaine, methaqualone, cannabis and opioids
  • A drop of oxygen saturations below 85% continuously for longer than five minutes during the baseline rPSG
  • Professional driver

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03127800


Locations
United Kingdom
Papworth Hospital NHS Foundation Trust
Papworth Everard, Cambridgeshire, United Kingdom, CB23 3RE
Sponsors and Collaborators
Papworth Hospital NHS Foundation Trust
Investigators
Study Director: Ian Smith, MBBS Papworth Hospital NHS Foundation Trust
Principal Investigator: Martina Mason, MBBS Papworth Hospital NHS Foundation Trust

Publications:
Koo, CY. Respiratory effects of opioids in perioperative medicine. The Open Anesthesiology Journal (Suppl 1-M6):23-4. 2011.
Scottish Intercollegiate Guidelines Network. Management of Obstructive Sleep Apnoea/Hypopnoea Syndrome in Adults. A national clinical guideline. (Guideline Number 73). 2003.
American Pain Society. Principles of analgesic use in the treatment of acute pain and cancer pain. 1999.

Responsible Party: Papworth Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03127800     History of Changes
Other Study ID Numbers: P01911
First Posted: April 25, 2017    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to make individual participant data available

Keywords provided by Papworth Hospital NHS Foundation Trust:
Obstructive Sleep Apnoea
Morphine sulphate
Sleep Disordered Breathing
Central Sleep Apnoea
Hypoxaemia
Hypercapnia
Cheyne-Stokes Respiration
Analgesia
Respiration
Apnoea-Hypopnea Index
Oxygen Desaturation Index
Oximetry
Respiratory Polygraphy
Polysomnography

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents