Topical Morphine for Analgesia in Patients With Skin Grafts

NCT00362219 | Withdrawn Phase 3

• 1 other identifier: RMC-2468.CTIL
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Skin Transplantation; Pain

Keywords

topical; morphine; pain; skin-wound; skin-graft; peripheral analgesia; burn

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Pain Score

  24 hours after surgery

• Time course of analgesia for each drug concentration

  First 24 hours after surgery

• Side effects

  First 24 hours after surgery

• Supplementary analgesic medications

  First 24 hours after surgery

• Analgesic medicine from 2nd post-operative day until dressings are removed.

  Day 2 post-surgery through 12th post-op day on average

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Gel with no active ingredient

Other: Placebo

Morphine .25 mg

ACTIVE COMPARATOR

Gel with 0.25 mg morphine per 100cm2 square of wound

Drug: Morphine - .25 mg

Morphine - .75 mg.

ACTIVE COMPARATOR

Gel with 0.75 mg morphine per 100cm2 square of wound.

Drug: Morphine

Morphine 1.25 mg.

ACTIVE COMPARATOR

Gel with 1.25 mg morphine per 100cm2 square of wound.

Drug: Morphine

Interventions

Placebo OTHER

Gel with no active ingredient.

Placebo

Morphine - .25 mg DRUG

gel with 0.25 mg morphine per 100cm2 square of wound.

Morphine .25 mg

Morphine DRUG

Gel with 0.75 mg morphine per 100cm2 square of wound.

Morphine - .75 mg.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rambam Health Care Campus: lead

Study Sites (1)

Department of Plastic Surgery, Rambam Medical Center

Haifa, 31096, Israel

Location

Related 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. doi: 10.1016/s0304-3959(98)00211-5.

  PMID: 10204724 BACKGROUND

• 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.

  PMID: 1653901 BACKGROUND

• 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.

  PMID: 16256893 BACKGROUND

• 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.

  PMID: 15120772 BACKGROUND

• 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.

  PMID: 10568861 BACKGROUND

• 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.

  PMID: 15733803 BACKGROUND

• 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.

  PMID: 12894165 BACKGROUND

MeSH Terms

Conditions

Pain; Burns

Interventions

Morphine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Wounds and Injuries

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

• Yehuda Ullman, M.D.

  Rambam Health Care Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Plastic Surgery Department

Study Record Dates

• First Submitted: August 8, 2006
• First Posted: August 9, 2006
• Study Start: January 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: May 3, 2022

Record last verified: 2022-04

Locations

IL (1)