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

NCT01082471 | Completed Phase 3

• 2 other identifiers: M6G0222005-001690-99
• Study Type: interventional
• Target: 517
• Locations: 6 countries
• Sites: 7

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.

Conditions

Postoperative Pain

Keywords

Morphine 6-glucuronide; Morphine; Patient Controlled Analgesia; Post Operative Nausea and Vomiting

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of nausea

  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.

  The 6-18 hour period after titration to pain relief

Secondary Outcomes (4)

• Analgesic effect

  0-48 hours after titration to pain relief

• The incidence and severity of nausea

  0-48 hours

• The incidence and severity of vomiting

  0-48 hours

• The amounts of study drug required to achieve a baseline pain severity score of ≤ 3

  60-30mins before close of surgery to time 0.

Study Arms (2)

M6G

EXPERIMENTAL

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

Morphine

ACTIVE COMPARATOR

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

Interventions

Morphine 6-glucuronide DRUG

M6G

Morphine DRUG

Morphine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Paion UK Ltd.: lead
• Chiltern International Ltd.: collaborator
• HFL Ltd.: collaborator

Study Sites (7)

Teaching Hospital Bulovka, Department of Urology

Prague, 180 00, Czechia

Location

Anaesthetisia - Resuscitation Department, Tenon Hospital

Paris, Cedex 20, 75970, France

Location

Universitätsklinikum Bonn, Klinik und Poliklinik f. Anaesthesiologie

Bonn, 53105, Germany

Location

Department of Anaesthesiology, Leiden University Medical Centre

Leiden, 2300 RC, Netherlands

Location

Ii Klinika Anestezjologii i It

Lublin, 20-081, Poland

Location

Intensive Care Unit, Level 5, Western Infirmary,

Glasgow, Renfrewshire, G11 6NT, United Kingdom

Location

St John's Hospital

Livingston, West Lothian, EH54 6PP, United Kingdom

Location

MeSH Terms

Conditions

Pain, Postoperative; Vomiting

Interventions

morphine-6-glucuronide; Morphine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Alexander Binning, M.D.

  Intensive Care Unit, Level 5, Western Infirmary, Glasgow, G11 6NT

  PRINCIPAL INVESTIGATOR

• James Lees, B.Sc.

  Paion UK Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 5, 2010
• First Posted: March 8, 2010
• Study Start: November 1, 2005
• Primary Completion: November 1, 2006
• Study Completion: December 1, 2006
• Last Updated: August 29, 2023

Record last verified: 2023-08

Locations

NL (1); GB (2); CZ (1); PL (1); DE (1); FR (1)