Clinical trial NCT01082471: An Efficacy and Safety Study to Compare Morphine 6-glucuronide (M6G) and Morphine in Patients Suffering With Post-Operative Pain for at Least 24 Hours
Official title: A Randomised Double-blind Study to Compare the Analgesic Efficacy and Safety Profiles of M6G and Morphine, as a Loading Dose Followed by PCA, in Patients Suffering Moderate to Severe Post-operative Pain Requiring PCA for at Least 24 Hours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Pain
Keywords: Morphine 6-glucuronide
Morphine
Patient Controlled Analgesia
Post Operative Nausea and Vomiting
Lead sponsor: Paion UK Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Chiltern International Ltd.
name: HFL Ltd.
First posted: 2010-03-08
Enrollment: 517
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the incidence and severity of nausea in the study treatment groups, during the 18-hour period starting 6 hours after titration to pain relief; following confirmation of the assumption of non-inferiority between the two groups of pain relief over the 24 hour post-operative period. Pain relief and nausea will be determined by measuring the areas under the curves of pain intensity and nausea verbal rating scale scores.


Eligibility criteria: Inclusion Criteria:

* Male or female patients undergoing any of the following elective surgical procedures that, in the Investigator's opinion, would have required the use of post-operative patient controlled analgesia for a minimum of 24 hours:
* Abdominal hysterectomy with the exception of laparoscopic procedures.
* Bowel / gastrointestinal (GI) surgery
* Major urological surgery
* Aged ≥ 18 years
* American Society of Anesthesiologists (ASA) grades I to III
* If female, the patient had to be post-menopausal (last menstruation \> 1 year previously), or surgically sterile (e.g. full hysterectomy or tubal ligation). If neither of these was the case, she had to use adequate contraception (i.e. hormonal contraceptive, intrauterine device (IUD), or a double barrier method) and to have a negative urine pregnancy test during the 24-hours prior to surgery.
* Provide written informed consent to participate in the trial prior to surgery.

Exclusion Criteria:

* The patient was pregnant or lactating.
* Had a known sensitivity to morphine or other opiates, or a medical condition such that opiates were contraindicated.
* Had a known sensitivity to paracetamol, or a medical condition such that paracetamol was contraindicated.
* Had received any investigational drug within the 90 days prior to the start of the study, or was scheduled to receive one during the study period.
* Had been involved in any previous M6G study.
* Had a documented history or current evidence of alcohol or drug abuse within the year prior to screening.
* Had clinically significant findings on pre-treatment evaluations (e.g. laboratory results, electrocardiograms, medical history, physical examination) that, in the Investigator's opinion, should have excluded them from the study.
* Had a concurrent disorder that resulted in excessive pain that, in the Investigator's opinion, would have interfered with the pain assessments during the study (e.g.severe rheumatoid arthritis, muscle dystrophy or neuropathic pain).
* Had a blood clotting disorder or other blood dyscrasias.
* Had requested the use of epidural or intrathecal anaesthesia techniques.
* Required the use of a local anaesthetic block and/or infiltration of wound sites.
* Required the concomitant use of opioids or non-steroidal anti-inflammatory drugs(NSAIDs) during the study due to an existing concurrent condition.
* Had a history of Left Ventricular Failure or compromised cardiovascular function, defined as New York Heart Association (NYHA) level 3.
* Had a history of severe renal impairment or a creatinine level \> 3 times the upper limit of normal.
* Was having surgery that would have prevented the use of oral or rectal paracetamol(iv administration of paracetamol was not allowed).
* Was expected to require prolonged ventilation after surgery.
* Was opioid tolerant or had a history of chronic opioid use.
* Had cognitive impairment that would, in the Investigator's opinion, have precluded participation or compliance with protocol defined procedures (i.e. use of PCA).

Primary outcomes:
measure: Incidence and severity of nausea
timeFrame: The 6-18 hour period after titration to pain relief
Secondary outcomes:
measure: Analgesic effect
timeFrame: 0-48 hours after titration to pain relief
measure: The incidence and severity of nausea
timeFrame: 0-48 hours
measure: The incidence and severity of vomiting
timeFrame: 0-48 hours
measure: The amounts of study drug required to achieve a baseline pain severity score of ≤ 3
timeFrame: 60-30mins before close of surgery to time 0.
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Teaching Hospital Bulovka, Department of Urology
city: Paris
country: France
facility: Anaesthetisia - Resuscitation Department, Tenon Hospital
state: Cedex 20
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Klinik und Poliklinik f. Anaesthesiologie
city: Leiden
country: Netherlands
facility: Department of Anaesthesiology, Leiden University Medical Centre
city: Lublin
country: Poland
facility: Ii Klinika Anestezjologii i It
city: Glasgow
country: United Kingdom
facility: Intensive Care Unit, Level 5, Western Infirmary,
state: Renfrewshire
city: Livingston
country: United Kingdom
facility: St John's Hospital
state: West Lothian
Study officials:
affiliation: Intensive Care Unit, Level 5, Western Infirmary, Glasgow, G11 6NT
name: Alexander Binning, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Paion UK Ltd.
name: James Lees, B.Sc.
role: STUDY_DIRECTOR
References: