Morphine in Moderate Obstructive Sleep Apnoea

NCT ID: NCT03127800

Last Updated: 2018-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-20

Study Completion Date

2018-06-06

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Obstructive Sleep Apnoea

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Morphine sulphate

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Morphine sulphate 10mg/ml

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Papworth Hospital NHS Foundation Trust

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ian Smith, MBBS

Role: STUDY_DIRECTOR

Papworth Hospital NHS Foundation Trust

Martina Mason, MBBS

Role: PRINCIPAL_INVESTIGATOR

Papworth Hospital NHS Foundation Trust

Locations

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Papworth Hospital NHS Foundation Trust

Papworth Everard, Cambridgeshire, United Kingdom

Site Status

Countries

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United Kingdom

References

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Duran J, Esnaola S, Rubio R, Iztueta A. Obstructive sleep apnea-hypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr. Am J Respir Crit Care Med. 2001 Mar;163(3 Pt 1):685-9. doi: 10.1164/ajrccm.163.3.2005065.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Koo, CY. Respiratory effects of opioids in perioperative medicine. The Open Anesthesiology Journal (Suppl 1-M6):23-4. 2011.

Reference Type BACKGROUND

Kushida CA, Littner MR, Morgenthaler T, Alessi CA, Bailey D, Coleman J Jr, Friedman L, Hirshkowitz M, Kapen S, Kramer M, Lee-Chiong T, Loube DL, Owens J, Pancer JP, Wise M. Practice parameters for the indications for polysomnography and related procedures: an update for 2005. Sleep. 2005 Apr;28(4):499-521. doi: 10.1093/sleep/28.4.499.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Scottish Intercollegiate Guidelines Network. Management of Obstructive Sleep Apnoea/Hypopnoea Syndrome in Adults. A national clinical guideline. (Guideline Number 73). 2003.

Reference Type BACKGROUND

Ostermeier AM, Roizen MF, Hautkappe M, Klock PA, Klafta JM. Three sudden postoperative respiratory arrests associated with epidural opioids in patients with sleep apnea. Anesth Analg. 1997 Aug;85(2):452-60. doi: 10.1097/00000539-199708000-00037. No abstract available.

Reference Type BACKGROUND
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Shaw IR, Lavigne G, Mayer P, Choiniere M. Acute intravenous administration of morphine perturbs sleep architecture in healthy pain-free young adults: a preliminary study. Sleep. 2005 Jun;28(6):677-82. doi: 10.1093/sleep/28.6.677.

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American Pain Society. Principles of analgesic use in the treatment of acute pain and cancer pain. 1999.

Reference Type BACKGROUND

Stradling J, Smith D, Radulovacki M, Carley D. Effect of ondansetron on moderate obstructive sleep apnoea, a single night, placebo-controlled trial. J Sleep Res. 2003 Jun;12(2):169-70. doi: 10.1046/j.1365-2869.2003.00342.x. No abstract available.

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Yarmush J, D'Angelo R, Kirkhart B, O'Leary C, Pitts MC 2nd, Graf G, Sebel P, Watkins WD, Miguel R, Streisand J, Maysick LK, Vujic D. A comparison of remifentanil and morphine sulfate for acute postoperative analgesia after total intravenous anesthesia with remifentanil and propofol. Anesthesiology. 1997 Aug;87(2):235-43. doi: 10.1097/00000542-199708000-00009.

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Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep. 1997 Sep;20(9):705-6. doi: 10.1093/sleep/20.9.705.

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Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29;328(17):1230-5. doi: 10.1056/NEJM199304293281704.

Reference Type BACKGROUND
PMID: 8464434 (View on PubMed)

Other Identifiers

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P01911

Identifier Type: -

Identifier Source: org_study_id

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