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Topical Morphine for Analgesia in Patients With Skin Grafts

R

Rambam Health Care Campus

Status and phase

Withdrawn
Phase 3

Conditions

Skin Transplantation
Pain

Treatments

Drug: Morphine
Other: Placebo
Drug: Morphine - .25 mg

Study type

Interventional

Funder types

Other

Identifiers

NCT00362219
RMC-2468.CTIL

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

0 participants in 4 patient groups, including a placebo group

Placebo
Placebo Comparator group
Description:
Gel with no active ingredient
Treatment:
Other: Placebo
Morphine .25 mg
Active Comparator group
Description:
Gel with 0.25 mg morphine per 100cm2 square of wound
Treatment:
Drug: Morphine - .25 mg
Morphine - .75 mg.
Active Comparator group
Description:
Gel with 0.75 mg morphine per 100cm2 square of wound.
Treatment:
Drug: Morphine
Drug: Morphine
Morphine 1.25 mg.
Active Comparator group
Description:
Gel with 1.25 mg morphine per 100cm2 square of wound.
Treatment:
Drug: Morphine
Drug: Morphine

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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