Topical Morphine for Analgesia in Patients With Skin Grafts

NCT ID: NCT00362219

Last Updated: 2022-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-31

Study Completion Date

2024-12-31

Brief Summary

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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

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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.

Conditions

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Skin Transplantation Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Placebo

Gel with no active ingredient

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Gel with no active ingredient.

Morphine .25 mg

Gel with 0.25 mg morphine per 100cm2 square of wound

Group Type ACTIVE_COMPARATOR

Morphine - .25 mg

Intervention Type DRUG

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

Morphine - .75 mg.

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

Group Type ACTIVE_COMPARATOR

Morphine

Intervention Type DRUG

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

Morphine 1.25 mg.

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

Group Type ACTIVE_COMPARATOR

Morphine

Intervention Type DRUG

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

Interventions

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Placebo

Gel with no active ingredient.

Intervention Type OTHER

Morphine - .25 mg

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

Intervention Type DRUG

Morphine

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

Intervention Type DRUG

Morphine

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rambam Health Care Campus

OTHER

Sponsor Role lead

Responsible Party

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Yehuda Ullmann MD

Head, Plastic Surgery Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yehuda Ullman, M.D.

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus

Locations

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Department of Plastic Surgery, Rambam Medical Center

Haifa, , Israel

Site Status

Countries

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Israel

References

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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.

Reference Type BACKGROUND
PMID: 10204724 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1653901 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16256893 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15120772 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10568861 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15733803 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12894165 (View on PubMed)

Other Identifiers

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RMC-2468.CTIL

Identifier Type: -

Identifier Source: org_study_id

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