AzTrials
AzTrials

Skin TransplantationPhase 3NCT00362219

Topical Morphine for Analgesia in Patients With Skin Grafts

A Phase 3 study testing Morphine - .25 mg and Morphine in people with Skin Transplantation and Pain, run by Rambam Health Care Campus at 1 site in Israel.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Skin Transplantation, Pain
What is being tested?
Morphine - .25 mg and Morphine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteIsrael
Study dates
Jan 2022to Dec 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

Israel1 site

  • Department of Plastic Surgery, Rambam Medical Center

    Haifa, 31096

Other trials in Israel

About this study

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.

Read the 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.

Being tested
Placebo, Morphine - .25 mg, Morphine
Keywords
topical, morphine, pain, skin-wound, skin-graft, peripheral analgesia, burn
Medical subject headings
Pain, Burns

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboOther

    Gel with no active ingredient.

  • Morphine - .25 mgDrug

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

  • MorphineDrug

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

  • MorphineDrug

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

Study groups in NCT00362219
Study groupRoleWhat they receive
PlaceboPlacebo comparatorGel with no active ingredient
Receives: Other: Placebo
Morphine .25 mgActive comparatorGel with 0.25 mg morphine per 100cm2 square of wound
Receives: Drug: Morphine - .25 mg
Morphine - .75 mg.Active comparatorGel with 0.75 mg morphine per 100cm2 square of wound.
Receives: Drug: Morphine
Morphine 1.25 mg.Active comparatorGel with 1.25 mg morphine per 100cm2 square of wound.
Receives: Drug: Morphine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 hours after application of the medication

Secondary outcomes (7)

  1. Pain Score

    Pain score at skin-donor site using an abbreviated form of the McGill Pain Questionnaire

    Measured: 24 hours after surgery

  2. Time course of analgesia for each drug concentration

    Time course of analgesia for each drug concentration

    Measured: First 24 hours after surgery

  3. Side effects

    Presence and severity of side effects: (a) central (nausea, vomiting, sedation, purities) and (b) local (burning, tingling, wheal, flare)

    Measured: First 24 hours after surgery

  4. Supplementary analgesic medications

    Concurrent, supplementary, "rescue", analgesic medication (i.v.or oral morphine), given during the first 24 hours post operatively

    Measured: First 24 hours after surgery

  5. 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).

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

  6. 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

    Measured: Twice daily from day 2 post-op until day 8 post-op

  7. Wound assessment

    Assessment of the wound once the dressings are removed

    Measured: Average day 12 post-operative

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2006 (estimated)
  2. Study startJan 2022 (estimated)
  3. Primary completionDec 2023 (estimated)
  4. Study completionDec 2024 (estimated)

Why it stopped: no patients were recrueted

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00362219
Sponsor's protocol ID
RMC-2468.CTIL
Status last verified
Apr 2022
First submitted
8 Aug 2006
Last updated
3 May 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 10204724

  • 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.

    PubMed 1653901

  • 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.

    PubMed 16256893

  • 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.

    PubMed 15120772

  • 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.

    PubMed 10568861

  • 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.

    PubMed 15733803

  • 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.

    PubMed 12894165

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Morphine - .25 mg and Morphine in people with Skin Transplantation and Pain, run by Rambam Health Care Campus at 1 site in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 3 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pain score in first 24 hours (time frame: 24 hours after application of the medication). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00362219, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in