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

This study has been completed.
Sponsor:
Collaborators:
Chiltern International Ltd.
HFL Ltd.
Information provided by:
Paion UK Ltd.
ClinicalTrials.gov Identifier:
NCT01082471
First received: March 5, 2010
Last updated: NA
Last verified: March 2010
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Postoperative Pain
Drug: Morphine 6-glucuronide
Drug: Morphine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Paion UK Ltd.:

Primary Outcome Measures:
  • Incidence and severity of nausea [ Time Frame: The 6-18 hour period after titration to pain relief ] [ Designated as safety issue: Yes ]
    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 were determined by measuring the areas under the curves of pain intensity and nausea verbal rating scale scores.


Secondary Outcome Measures:
  • Analgesic effect [ Time Frame: 0-48 hours after titration to pain relief ] [ Designated as safety issue: No ]

    To compare the analgesic effect of the study treatments using an Investigator- and patient-administered VRS-11 scale of pain intensity over the following time periods following achievement of baseline pain relief.

    1. 0-12 hours (AUCbaseline-12)
    2. 0-48 hours (AUCbaseline - 48)
    3. 12-24 hours (AUC12 - 24)
    4. 24-48 hours (AUC24 - 48) Pain levels will be compared using the AUC from baseline.

  • The incidence and severity of nausea [ Time Frame: 0-48 hours ] [ Designated as safety issue: Yes ]
    To compare the incidence and severity of nausea in the study treatment groups over the following time periods following achievement of baseline pain relief: 0-12 hours, 0-24 hours, 0-48 hours, 12-24 hours, 24-48 hours.

  • The incidence and severity of vomiting [ Time Frame: 0-48 hours ] [ Designated as safety issue: Yes ]
    To compare the incidence and severity of vomiting in the study treatment groups over the following time periods following achievement of baseline pain relief: 0-12 hours, 0-24 hours, 0-48 hours, 12-24 hours, 24-48 hours

  • The amounts of study drug required to achieve a baseline pain severity score of ≤ 3 [ Time Frame: 60-30mins before close of surgery to time 0. ] [ Designated as safety issue: No ]
    To compare the amounts of study drug required to achieve a baseline pain severity score of ≤ 3


Enrollment: 517
Study Start Date: November 2005
Study Completion Date: December 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: M6G
An initial slow bolus injection up to 60 min prior to end of surgery. If required, two additional slow bolus injections to achieve baseline pain relief. Continuing on PCA for a minimum of 24 hours.
Drug: Morphine 6-glucuronide
Active Comparator: Morphine
An initial slow bolus injection up to 60 min prior to end of surgery. If required, two additional slow bolus injections to achieve baseline pain relief. Continuing on PCA for a minimum of 24 hours.
Drug: Morphine

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01082471

Locations
Czech Republic
Teaching Hospital Bulovka, Department of Urology
Prague, Czech Republic, 180 00
France
Anaesthetisia - Resuscitation Department, Tenon Hospital
Paris, Cedex 20, France, 75970
Germany
Universitätsklinikum Bonn, Klinik und Poliklinik f. Anaesthesiologie
Bonn, Germany, 53105
Netherlands
Department of Anaesthesiology, Leiden University Medical Centre
Leiden, Netherlands, 2300 RC
Poland
Ii Klinika Anestezjologii i It
Lublin, Poland, 20-081
United Kingdom
Intensive Care Unit, Level 5, Western Infirmary,
Glasgow, Renfrewshire, United Kingdom, G11 6NT
St John's Hospital
Livingston, West Lothian, United Kingdom, EH54 6PP
Sponsors and Collaborators
Paion UK Ltd.
Chiltern International Ltd.
HFL Ltd.
Investigators
Principal Investigator: Alexander Binning, M.D. Intensive Care Unit, Level 5, Western Infirmary, Glasgow, G11 6NT
Study Director: James Lees, B.Sc. Paion UK Ltd.
  More Information

No publications provided

Responsible Party: Dr. Alexander Binning, Western Infirmary, Glasgow, NHS Scotland
ClinicalTrials.gov Identifier: NCT01082471     History of Changes
Other Study ID Numbers: M6G022, 2005-001690-99
Study First Received: March 5, 2010
Last Updated: March 5, 2010
Health Authority: Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Paion UK Ltd.:
Morphine 6-glucuronide
Morphine
Patient Controlled Analgesia
Post Operative Nausea and Vomiting

Additional relevant MeSH terms:
Pain, Postoperative
Stress, Psychological
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Behavioral Symptoms
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014