MelanomaPhase 3PRIMENCT05899465
Perioperative Treatment With Tranexamic Acid in Melanoma
A Phase 3 study testing Tranexamic acid and Saline in people with Melanoma, run by University of Aarhus at 5 sites in Denmark.
Trial summary
Surgery is a key element in the treatment of melanoma, and naturally linked with an inflammatory response and recruitment of innate immune cells. Although surgery has a favorable intent, surgery-induced inflammation, neutrophils in particular, may accelerate growth of local and systemic micrometastases. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Tranexamic acid and Saline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,204 participants
- Where
- 5 sitesDenmark
- Study dates
- 25 Aug 2023to 1 Sep 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients
- Diagnosed with invasive cutaneous melanoma (pathological stage/tumor grade ≥T2b), defined as either: Breslow thickness >1.0-2.0 mm with presence of ulceration or Breslow thickness >2.0 mm regardless of ulceration status.
- Eligible for surgery (wide local excision and sentinel lymph node biopsy).
- >/=18 years of age and </=80 years of age
- Signed Informed Consent Form
Who cannot join
- Patients
- With a prior history of invasive melanoma
- Thromboembolic events within the last 3 months
- Pregnancy
- Active breastfeeding
- Known allergy or hypersensitivity to TXA
Show all 9Show fewer
- Known and treated epilepsia or previous seizures
- eGFR 0-50
- Current use of tranexamic acid
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Karoline Kristjansen, MD contact
5 sites in 1 country
Denmark5 sites, 3 recruiting
- Recruiting
Aalborg University Hospital. Dept. of Plastic- and Breast Surgery.
Aalborg, North Denmark
Karoline Kristjansen, MD
- Recruiting
Aarhus University Hospital. Dept. of Plastic- and Breast Surgery
Aarhus, Central Jutland
Louise Bønnelykke-Behrndtz, MD, PhD
- Recruiting
Copgenhagen University Hospital, Rigshospitalet. Dept. of Plastic Surgery and Burns Treatment
Copenhagen
Linnea Langhans, MD, PhD
- Active, not recruiting
Copenhagen University Hospital, Herlev. Dept. of Plastic Surgery
Herlev
- Active, not recruiting
Sygehus Lillebælt, Vejle Hospital. Dept. of Plastic Surgery
Vejle
About this study
Official title: Perioperative Treatment With Tranexamic Acid in Melanoma; Prognostic and Treatment-related Impact of the Plasminogen-plasmin Pathway
Surgery is a key element in the treatment of melanoma, and naturally linked with an inflammatory response and recruitment of innate immune cells. Although surgery has a favorable intent, surgery-induced inflammation, neutrophils in particular, may accelerate growth of local and systemic micrometastases. Thus, improving cancer surgery and modulating the wound microenvironment in ways that benefit the patients is crucial.
Repurposing already approved drugs in a cancer setting has gained increasing interest in recent years. Interestingly, tranexamic acid was recently suggested as an anti-cancer drug, capable of reducing tumor growth in experimental animal models and reducing the viability of different melanoma cell lines.
As a novel approach, sponsor and investigators will conduct a Randomised Clinical Trial, using perioperative treatment with Tranexamic Acid, aiming to prevent the early relapses for patients with melanoma.
Read the detailed description
The objective of the proposed clinical trial is to test if perioperative treatment with tranexamic acid (TXA) reduces the early relapses and postoperative complications for patients with melanoma and evaluate perioperative inflammation and the prognostic- and treatment-related impact of the plasminogen-plasmin pathway from human blood- and tissue samples.
Primary aim:
To test if perioperative treatment with TXA is superior to placebo and reduces the early relapse rates, from 37% to 26%, for patients diagnosed with melanoma undergoing sentinel lymph node biopsy surgery.
Secondary aims:
- Evaluate safety and tolerability: defined as mild (abdominal pain, diarrhea, or nausea) or severe (thromboembolic events) adverse effects.
- Evaluate postoperative complications: defined as bleeding, seroma formation, and infections within the first three postoperative months.
- Estimate melanoma-specific survival probabilities and compare the two treatment groups.
Explorative:
From blood- and tissue samples, baseline and perioperative changes of factors associated with inflammation, fibrinolysis, metabolism, immune cell composition, and activation status will be monitored and factors will be associated with prognostic and treatment-related outcomes.
- Conditions
- Melanoma
- Being tested
- Tranexamic acid, Saline
- Keywords
- Melanoma, Tranexamic acid, Relapse, Cancer, Drug Repositioning, Surgery
- Medical subject headings
- Melanoma, Recurrence, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic acidDrug
A single preoperative intravenous dose and per os treatment postoperatively day 1 through 4
SalineDrug
A single preoperative intravenous dose and per os treatment postoperatively day 1 through 4
| Study group | Role | What they receive |
|---|---|---|
| Tranexamic Acid | Experimental | A single dose of TXA (15 mg/kg) administered intravenously 30 min (+/-15 min) before skin incision and subsequently, TXA (1000 mg) administered orally 4 and 8 hours post-surgery and TXA (1000 mg) 3 times daily through postoperative day 4. Receives: Drug: Tranexamic acid |
| Placebo | Placebo comparator | A single dose of saline matching the volume of the experimental arm treatment regiment (Saline) administered intravenously 30 min (+/-15 min) before skin incision and subsequently, placebo tablets (2 tabs.) administered orally 4 and 8 hours post-surgery and (2 tabs) 3 times daily through postoperative day 4. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in rate of relapse within two years when comparing treatment arms
Histopathological confirmed relapse, defined as either local, regional (in transit or lymph node) or systemic relapses. Systemic metastases suspected on PET / CT/ MR will be used if a biopsy is not possible. Based on the primary endpoint, we will calculate the relapse risk proportions for each treatment arm as a binary outcome.
The date of relapse or completed follow-up is noted and the relapse-free period is defined as the date of wide local excision and sentinel lymph node biopsy until the date of either the first confirmed relapse or the date of completed two-year follow-up without relapse.
Measured: 2 year follow-up
Secondary outcomes (5)
Incidence of treatment-related adverse events
Adverse events summarised according to grade:
Mild: defined as the patient's report of abdominal pain, diarrhea, or nausea. Severe: thromboembolic events, verified radiologically.
Measured: 6 months follow-up
Assessment of incidens of postoperative complications
Postoperative complications, summarised according to the type and postoperative timepoint, is defined as binary outcomes:
Bleeding: defined as a drained or surgically removed hematoma or suggillation of blood to the skin around the operated area, occurring within the first 10 days post-surgery.
Seroma: drained seroma, during the period from end of surgery through 3 months post-surgery.
Infection: local wound infection, treated with antibiotics or surgical intervention, during the period from end of surgery through 3 months post-surgery.
Measured: 3 months follow-up
Melanoma-specific survival
Time to event estimates:
Defined as the period from the date of surgery (wide local excision and sentinel lymph node biopsy) to the date of death from suspected systemic melanoma (histopathologically confirmed relapse or systemic metastases suspected on PET / CT / MR) or the date of completed 2 years follow-up.
Measured: 2 year follow-up
Overall survival
Time to event estimates:
Defined as the period from the date of surgery (re-excision and sentinel node) to the date of death from all causes or the date of finalised 2 years follow-up.
Measured: 2 year follow-up
Relapse free survival
Time to event estimates:
Defined as the period from the date of surgery (re-excision and sentinel node) to the date of histopathologically confirmed relapse (local, regional or systemic), death from all causes or the data or completed 2 years follow-up.
Measured: 2 year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start25 Aug 2023
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel, two-arm, randomized, blinded Danish multi-center trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,204 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Central Denmark Region
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05899465
- Sponsor's protocol ID
- PRIME
- Acronym
- PRIME
- Status last verified
- Mar 2025
- First submitted
- 4 Apr 2023
- Last updated
- 18 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Entirely anonymized data will be shared only upon reasonable request made to the sponsor and evaluated by the steering committee. Researchers requesting access are required to sign a data access agreement assuring that data will only be utilized for a predetermined and accepted purpose.
Publications
Kristjansen KA, Engel Krag A, Schmidt H, Holmich LR, Bonnelykke-Behrndtz ML. Perioperative treatment with tranexamic acid in melanoma (PRIME): protocol for a Danish multicentre randomised controlled trial investigating the prognostic and treatment-related impact of the plasminogen-plasmin pathway. BMJ Open. 2024 Feb 2;14(2):e077012. doi: 10.1136/bmjopen-2023-077012.
PubMed 38309757
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Treatment With Tranexamic Acid in Melanoma; Prognostic and Treatment-related Impact of the Plasminogen-plasmin Pathway
- ClinicalTrials.gov ID
- NCT05899465
- Acronym / sponsor ID
- PRIME / PRIME
- Conditions
- Melanoma
- Keywords
- Melanoma, Tranexamic acid, Relapse, Cancer, Drug Repositioning, Surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,204 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Central Denmark Region
- Study start
- 25 Aug 2023 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 12 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Surgery is a key element in the treatment of melanoma, and naturally linked with an inflammatory response and recruitment of innate immune cells. Although surgery has a favorable intent, surgery-induced inflammation, neutrophils in particular, may accelerate growth of local and systemic micrometastases. Thus, improving cancer surgery and modulating the wound microenvironment in ways that benefit the patients is crucial.
Repurposing already approved drugs in a cancer setting has gained increasing interest in recent years. Interestingly, tranexamic acid was recently suggested as an anti-cancer drug, capable of reducing tumor growth in experimental animal models and reducing the viability of different melanoma cell lines.
As a novel approach, sponsor and investigators will conduct a Randomised Clinical Trial, using perioperative treatment with Tranexamic Acid, aiming to prevent the early relapses for patients with melanoma.
Detailed description
The objective of the proposed clinical trial is to test if perioperative treatment with tranexamic acid (TXA) reduces the early relapses and postoperative complications for patients with melanoma and evaluate perioperative inflammation and the prognostic- and treatment-related impact of the plasminogen-plasmin pathway from human blood- and tissue samples.
Primary aim:
To test if perioperative treatment with TXA is superior to placebo and reduces the early relapse rates, from 37% to 26%, for patients diagnosed with melanoma undergoing sentinel lymph node biopsy surgery.
Secondary aims:
- Evaluate safety and tolerability: defined as mild (abdominal pain, diarrhea, or nausea) or severe (thromboembolic events) adverse effects.
- Evaluate postoperative complications: defined as bleeding, seroma formation, and infections within the first three postoperative months.
- Estimate melanoma-specific survival probabilities and compare the two treatment groups.
Explorative:
From blood- and tissue samples, baseline and perioperative changes of factors associated with inflammation, fibrinolysis, metabolism, immune cell composition, and activation status will be monitored and factors will be associated with prognostic and treatment-related outcomes.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel, two-arm, randomized, blinded Danish multi-center trial
| Arm | Type | Receives |
|---|---|---|
| Tranexamic Acid | Experimental | Drug: Tranexamic acidA single dose of TXA (15 mg/kg) administered intravenously 30 min (+/-15 min) before skin incision and subsequently, TXA (1000 mg) administered orally 4 and 8 hours post-surgery and TXA (1000 mg) 3 times daily through postoperative day 4. |
| Placebo | Placebo comparator | Drug: SalineA single dose of saline matching the volume of the experimental arm treatment regiment (Saline) administered intravenously 30 min (+/-15 min) before skin incision and subsequently, placebo tablets (2 tabs.) administered orally 4 and 8 hours post-surgery and (2 tabs) 3 times daily through postoperative day 4. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients
- Diagnosed with invasive cutaneous melanoma (pathological stage/tumor grade ≥T2b), defined as either: Breslow thickness >1.0-2.0 mm with presence of ulceration or Breslow thickness >2.0 mm regardless of ulceration status.
- Eligible for surgery (wide local excision and sentinel lymph node biopsy).
- >/=18 years of age and </=80 years of age
- Signed Informed Consent Form
Key exclusion criteria (9 listed)
- Patients
- With a prior history of invasive melanoma
- Thromboembolic events within the last 3 months
- Pregnancy
- Active breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tranexamic acidA single preoperative intravenous dose and per os treatment postoperatively day 1 through 4 | Drug | Tranexamic Acid |
| SalineA single preoperative intravenous dose and per os treatment postoperatively day 1 through 4 | Drug | Placebo |
Primary outcome
Difference in rate of relapse within two years when comparing treatment arms
Time frame: 2 year follow-up
Histopathological confirmed relapse, defined as either local, regional (in transit or lymph node) or systemic relapses. Systemic metastases suspected on PET / CT/ MR will be used if a biopsy is not possible. Based on the primary endpoint, we will calculate the relapse risk proportions for each treatment arm as a binary outcome. The date of relapse or completed follow-up is noted and the relapse-free period is defined as the date of wide local excision and sentinel lymph node biopsy until the date of either the first confirmed relapse or the date of completed two-year follow-up without relapse.
5 secondary outcomes
Incidence of treatment-related adverse events
Time frame: 6 months follow-up
Assessment of incidens of postoperative complications
Time frame: 3 months follow-up
Melanoma-specific survival
Time frame: 2 year follow-up
Overall survival
Time frame: 2 year follow-up
Relapse free survival
Time frame: 2 year follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2025.
- Derived from this study: PubMed 38309757Kristjansen KA, Engel Krag A, Schmidt H, Holmich LR, Bonnelykke-Behrndtz ML. Perioperative treatment with tranexamic acid in melanoma (PRIME): protocol for a Danish multicentre randomised controlled trial investigating the prognostic and treatment-related impact of the plasminogen-plasmin pathway. BMJ Open. 2024 Feb 2;14(2):e077012. doi: 10.1136/bmjopen-2023-077012.
- Individual participant dataSharing planned: Yes. Entirely anonymized data will be shared only upon reasonable request made to the sponsor and evaluated by the steering committee. Researchers requesting access are required to sign a data access agreement assuring that data will only be utilized for a predetermined and accepted purpose.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Karoline Kristjansen, MD contact
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tranexamic acid and Saline in people with Melanoma, run by University of Aarhus at 5 sites in Denmark.
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 9 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: looking for participants now, as of the sponsor's last update on 18 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marie Louise Bønnelykke-Behrndtz, MD, PhD (+45 78 45 00 00, marboe@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in rate of relapse within two years when comparing treatment arms (time frame: 2 year follow-up). 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 NCT05899465, which also lists 1 linked publication.
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 18 Mar 2025.