Morphine in Moderate Obstructive Sleep Apnoea (MIMOSA)

November 28, 2018 updated by: Papworth Hospital NHS Foundation Trust

The Effect of Acute Intravenous Morphine Administration on Sleep Disordered Breathing (SDB) in Patients With Moderate Obstructive Sleep Apnoea (OSA): A Paired Design Trial

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Enrollment (Actual)

6

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Cambridgeshire
      • Papworth Everard, Cambridgeshire, United Kingdom, CB23 3RE
        • Papworth Hospital NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Morphine sulphate 10mg/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Change in AHI from baseline Respiratory Polygraphy (rPSG) through to completion of study at overnight visit, within 4 months of baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Change in arterial oxygen desaturations from baseline Respiratory Polygraphy (rPSG) through to completion of study at overnight visit, within 4 months of baseline
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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 and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 20, 2016

Primary Completion (Actual)

November 4, 2017

Study Completion (Actual)

June 6, 2018

Study Registration Dates

First Submitted

June 13, 2016

First Submitted That Met QC Criteria

April 20, 2017

First Posted (Actual)

April 25, 2017

Study Record Updates

Last Update Posted (Actual)

November 29, 2018

Last Update Submitted That Met QC Criteria

November 28, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P01911

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is no plan to make individual participant data available

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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