Topical Morphine for Analgesia in Patients With Skin Grafts

Pain Clinical Trial

Official title:

Topical Morphine for Analgesia in Patients With Skin Grafts

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00362219
• Other study ID #: RMC-2468.CTIL
• Status: Withdrawn
• Phase: Phase 3
• Start date: January 2022
• Est. completion date: December 2024

Study information

• Verified date: April 2022
• Source: Rambam Health Care Campus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Pain
• Skin Transplantation

Intervention

Other:
• Placebo
Gel with no active ingredient.

Drug:
• Morphine - .25 mg
gel with 0.25 mg morphine per 100cm2 square of wound.
• Morphine
Gel with 0.75 mg morphine per 100cm2 square of wound.
• Morphine
Gel with 1.25 mg morphine per 100cm2 square of wound.

Locations

Country	Name	City	State
Israel	Department of Plastic Surgery, Rambam Medical Center	Haifa

Sponsors (1)

Lead Sponsor	Collaborator
Rambam Health Care Campus

Country where clinical trial is conducted

Israel, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

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

Zeppetella G, Ribeiro MD. Morphine in intrasite gel applied topically to painful ulcers. J Pain Symptom Manage. 2005 Feb;29(2):118-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain score in first 24 hours	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.	24 hours after application of the medication
Secondary	Pain Score	Pain score at skin-donor site using an abbreviated form of the McGill Pain Questionnaire	24 hours after surgery
Secondary	Time course of analgesia for each drug concentration	Time course of analgesia for each drug concentration	First 24 hours after surgery
Secondary	Side effects	Presence and severity of side effects: (a) central (nausea, vomiting, sedation, purities) and (b) local (burning, tingling, wheal, flare)	First 24 hours after surgery
Secondary	Supplementary analgesic medications	Concurrent, supplementary, "rescue", analgesic medication (i.v.or oral morphine), given during the first 24 hours post operatively	First 24 hours after surgery
Secondary	Analgesic medicine from 2nd post-operative day until dressings are removed.	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).	Day 2 post-surgery through 12th post-op day on average
Secondary	Pain score collection	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	Twice daily from day 2 post-op until day 8 post-op
Secondary	Wound assessment	Assessment of the wound once the dressings are removed	Average day 12 post-operative