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

Abstract

Introduction: Inflammation is a hallmark of cancer and is involved in tumour growth and dissemination. However, the hallmarks of cancer are also the hallmarks of wound healing, and modulating the wound inflammatory response and immune contexture in relation to cancer surgery may represent effective targets of therapies.Repurposing anti-inflammatory drugs in a cancer setting has gained increasing interest in recent years. Interestingly, the known and thoroughly tested antifibrinolytic drug tranexamic acid reduces the risk of bleeding, but it is also suggested to play important roles in anti-inflammatory pathways, improving wound healing and affecting anti-carcinogenic mechanisms.As a novel approach, we will conduct a randomised controlled trial using perioperative treatment with tranexamic acid, aiming to prevent early relapses by >10% for patients with melanoma.

Methods and analysis: Design: investigator-initiated parallel, two-arm, randomised, blinded, Danish multicentre superiority trial.

Patients: ≥T2 b melanoma and eligible for sentinel lymph node biopsy (n=1204).Project drug: tranexamic acid or placebo.

Treatment: before surgery (intravenous 15 mg/kg) and daily (peroral 1000 mg x 3) through postoperative day 4.

Primary outcome: relapse within 2 years after surgery.Primary analysis: risk difference between the treatment arms (χ² test).

Secondary outcomes: postoperative complications, adverse events and survival.Inclusion period: summer 2023 to summer 2026.

Ethics and dissemination: The trial will be initiated during the summer of 2023 and is approved by the National Committee on Health Research Ethics, the Danish Medicine Agency, and registered under the Data Protection Act. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Patients included in the study will adhere to normal Danish treatment protocols and standards of care, and we expect only mild and temporary side effects. Positive and negative results will be published in peer-reviewed journals, with authorships adhering to the Vancouver rules.

Trial registration number: NCT05899465; ClinicalTrials.gov Identifier.

Keywords: Clinical trials; Dermatological tumours; Randomized Controlled Trial; Surgical dermatology.

Figure 1

Treatment Regimen: treatment arm includes intravenous TXA preoperatively, and subsequently, TXA orally 4 and 8 hours postoperatively, and TXA 3 times daily through postoperative day 4. The placebo arm includes saline in matching doses. TXA, tranexamic acid.

Figure 2

Participant timeline and assessments: illustration of data collection with timepoints in relation to surgery and disclosure of how data is obtained. BMI, Body Mass Index; NSAID, Non-steroidal anti-inflammatory drugs; AE, Adverse Events; SAE, Serious Adverse Events; Re-exc., Re-excision.