Topical Morphine for Analgesia in Patients With Skin Grafts - Full Text View

Sponsor:	Rambam Health Care Campus
Information provided by (Responsible Party):	y_ullmann, Rambam Health Care Campus
ClinicalTrials.gov Identifier:	NCT00362219

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 III

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

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

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:

Krajnik M, Zylicz Z, Finlay I, Luczak J, van Sorge AA. Potential uses of topical opioids in palliative care--report of 6 cases. Pain. 1999 Mar;80(1-2):121-5.

Stein C, Comisel K, Haimerl E, Yassouridis A, Lehrberger K, Herz A, Peter K. Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med. 1991 Oct 17;325(16):1123-6.

Porzio G, Aielli F, Verna L, Cannita K, Marchetti P, Ficorella C. Topical morphine in the treatment of painful ulcers. J Pain Symptom Manage. 2005 Oct;30(4):304-5. No abstract available.

Ribeiro MD, Joel SP, Zeppetella G. The bioavailability of morphine applied topically to cutaneous ulcers. J Pain Symptom Manage. 2004 May;27(5):434-9.

Stein A, Yassouridis A, Szopko C, Helmke K, Stein C. Intraarticular morphine versus dexamethasone in chronic arthritis. Pain. 1999 Dec;83(3):525-32.

Zeppetella G, Ribeiro MD. Morphine in intrasite gel applied topically to painful ulcers. J Pain Symptom Manage. 2005 Feb;29(2):118-9. No abstract available.

Stein C, Schafer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med. 2003 Aug;9(8):1003-8. Review.

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
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotics

ClinicalTrials.gov processed this record on February 09, 2012