Clinical trial NCT00362219: Topical Morphine for Analgesia in Patients With Skin Grafts
Official title: Topical Morphine for Analgesia in Patients With Skin Grafts
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Skin Transplantation
Pain
Keywords: topical
morphine
pain
skin-wound
skin-graft
peripheral analgesia
burn
Lead sponsor: Rambam Health Care Campus
Sponsor class: OTHER
First posted: 2006-08-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Pain score in first 24 hours
timeFrame: 24 hours after application of the medication
Secondary outcomes:
measure: Pain Score
timeFrame: 24 hours after surgery
measure: Time course of analgesia for each drug concentration
timeFrame: First 24 hours after surgery
measure: Side effects
timeFrame: First 24 hours after surgery
measure: Supplementary analgesic medications
timeFrame: First 24 hours after surgery
measure: Analgesic medicine from 2nd post-operative day until dressings are removed.
timeFrame: Day 2 post-surgery through 12th post-op day on average
measure: Pain score collection
timeFrame: Twice daily from day 2 post-op until day 8 post-op
measure: Wound assessment
timeFrame: Average day 12 post-operative
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Department of Plastic Surgery, Rambam Medical Center
Study officials:
affiliation: Rambam Health Care Campus
name: Yehuda Ullman, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/s0304-3959(98)00211-5.
citation: 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. doi: 10.1056/NEJM199110173251602.
citation: 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. doi: 10.1016/j.jpainsymman.2005.08.011. No abstract available.
citation: 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. doi: 10.1016/j.jpainsymman.2003.09.011.
citation: Stein A, Yassouridis A, Szopko C, Helmke K, Stein C. Intraarticular morphine versus dexamethasone in chronic arthritis. Pain. 1999 Dec;83(3):525-532. doi: 10.1016/S0304-3959(99)00156-6.
citation: Zeppetella G, Ribeiro MD. Morphine in intrasite gel applied topically to painful ulcers. J Pain Symptom Manage. 2005 Feb;29(2):118-9. doi: 10.1016/j.jpainsymman.2004.12.006. No abstract available.
citation: Stein C, Schafer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med. 2003 Aug;9(8):1003-8. doi: 10.1038/nm908.