Topical Morphine for Analgesia in Patients With Skin Grafts

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
y_ullmann, Rambam Health Care Campus
ClinicalTrials.gov Identifier:
NCT00362219
First received: August 8, 2006
Last updated: October 27, 2011
Last verified: October 2011
  Purpose

The management of pain endured by patients after skin grafting is complex. Pain is the single most distressing symptom but as it is difficult to manage, it is often under-treated. These patients may experience pain from two types of wound: the original injury and from "skin-donor" sites, areas of healthy skin from which skin is surgically removed and used to cover the original injury. As the section of skin which is removed is standardized, the wound created at the donor site is uniform and so provides a model of an acute wound.

Opioids (such as morphine) are the backbone of treating the moderate to severe pain experienced by any patient. But due to their potentially severe side effects and that some patients do not experience sufficient relief from the treatment, optimal treatment schedules are still being sought after.

Topically applied morphine has provided effective and safe analgesia in several clinical models. We, therefore, wish to apply this treatment modality onto skin-graft donor wounds. If found to be effective this could be an appealing non-invasive method to treat the pain of this type of wound.


Condition Intervention Phase
Skin Transplantation
Pain
Other: Placebo
Drug: Morphine - .25 mg
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, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Topical Morphine for Analgesia in Patients With Skin Grafts

Resource links provided by NLM:


Further study details as provided by Rambam Health Care Campus:

Primary Outcome Measures:
  • Pain score in first 24 hours [ Time Frame: 24 hours after application of the medication ] [ Designated as safety issue: No ]
    Sum of the differences in pain scores between the skin-donor site vs. original injury site taken over a 24 hour period after application of the medication.


Secondary Outcome Measures:
  • Pain Score [ Time Frame: 24 hours after surgery ] [ Designated as safety issue: No ]
    Pain score at skin-donor site using an abbreviated form of the McGill Pain Questionnaire

  • Time course of analgesia for each drug concentration [ Time Frame: First 24 hours after surgery ] [ Designated as safety issue: No ]
    Time course of analgesia for each drug concentration

  • Side effects [ Time Frame: First 24 hours after surgery ] [ Designated as safety issue: Yes ]
    Presence and severity of side effects: (a) central (nausea, vomiting, sedation, purities) and (b) local (burning, tingling, wheal, flare)

  • Supplementary analgesic medications [ Time Frame: First 24 hours after surgery ] [ Designated as safety issue: No ]
    Concurrent, supplementary, "rescue", analgesic medication (i.v.or oral morphine), given during the first 24 hours post operatively

  • Analgesic medicine from 2nd post-operative day until dressings are removed. [ Time Frame: Day 2 post-surgery through 12th post-op day on average ] [ Designated as safety issue: No ]
    Analgesic medication (type and dose), given from the second post-operative day until dressings are removed for the first time (= the 12th post-operataive day, on average).

  • Pain score collection [ Time Frame: Twice daily from day 2 post-op until day 8 post-op ] [ Designated as safety issue: No ]
    Pain scores at donor and original injury, twice daily, from the second post-operative day until dressings are removed for the first time - up until 8th post-op day

  • Wound assessment [ Time Frame: Average day 12 post-operative ] [ Designated as safety issue: No ]
    Assessment of the wound once the dressings are removed


Enrollment: 40
Study Start Date: December 2006
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Gel with no active ingredient
Other: Placebo
Gel with no active ingredient.
Active Comparator: Morphine .25 mg
Gel with 0.25 mg morphine per 100cm2 square of wound
Drug: Morphine - .25 mg
gel with 0.25 mg morphine per 100cm2 square of wound.
Active Comparator: Morphine - .75 mg.
Gel with 0.75 mg morphine per 100cm2 square of wound.
Drug: Morphine
Gel with 0.75 mg morphine per 100cm2 square of wound.
Active Comparator: Morphine 1.25 mg.
Gel with 1.25 mg morphine per 100cm2 square of wound.
Drug: Morphine
Gel with 1.25 mg morphine per 100cm2 square of wound.

Detailed Description:

Administration of morphine into the knee joint is the best-studied clinical procedure documenting the use of topically-applied opioids. When 1-5 mg morphine were injected into the knee joint, patients experienced pain relief for up to 24 hours, whereas similar doses given systemically (i.e. intravenously) were effective for 2-4 hours. Furthermore, the analgesic effect was reversed when the opioid antagonist naloxone was injected into the knee joint. Both these findings indicate that the effect is mediated by local opioid receptors in the knee joint.

Peripheral analgesic effects of opioids are not detectable in normal tissue but appear minutes to hours after initiation of inflammation. This suggests that opioid receptors are already present in the peripheral nerve terminals but under normal conditions they are not functional.

Research on application of opioids to skin wounds is very sparse and has primarily been performed in palliative care patients. These reports demonstrate that topical opioid gel (morphine or diamorphine) provided rapid and effective relief. In some patients pain subsided within 20 minutes after application with a long-lasting (7-8 hours) effect. Fundamental aspects regarding topical application of opioids onto skin wounds are still lacking. For example, issues such as optimal dose and dose-effect relationships have not been investigated. We hope to determine these in this study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients undergoing skin-grafting
  • American Society of Anesthesiologists (ASA) classification I-II
  • Written consent
  • Either sex
  • Able to self-asses and report their pain level

Exclusion Criteria:

  • Alcohol abuse or addiction - current
  • Opioids and benzodiazepines abuse - life time
  • Known hypersensitivity to morphine
  • Major renal or hepatic dysfunction
  • Pregnancy or lactation
  • Sleep-apnoea-syndrome
  • Diabetes
  • Participation in other clinical studies
  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: NCT00362219

Locations
Israel
Department of Plastic Surgery, Rambam Medical Center
Haifa, Israel, 31096
Sponsors and Collaborators
Rambam Health Care Campus
Investigators
Principal Investigator: Yehuda Ullman, M.D. Rambam Health Care Campus
  More Information

Publications:
Responsible Party: y_ullmann, Head, Plastic Surgery Department, Rambam Health Care Campus
ClinicalTrials.gov Identifier: NCT00362219     History of Changes
Other Study ID Numbers: RMC-2468.CTIL
Study First Received: August 8, 2006
Last Updated: October 27, 2011
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Rambam Health Care Campus:
topical
morphine
pain
skin-wound
skin-graft
peripheral analgesia
burn

Additional relevant MeSH terms:
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 25, 2014