A Study of Direct Oral Anticoagulants in Patients with Painful Venous Malformations with Localized Intravascular Coagulation

NCT06729034 | Not Yet Recruiting Phase 2

• 1 other identifier: 2024-511930-11-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

There are two parts of the study. In Part 1, the invesitgaotrs want to investigate whether treatment with apixaban improves pain and quality of life in patients with painful venous malformations The participants are randomized to different treatment orders of the two treatment periods with apixaban and placebo. Arm 1 starts apixaban followed by placebo and arm 2 starts with placebo followed by apixaban. Between the treatment sequences there will be a washout period of minimum one week. The participants will register pain and use og pain medication in a diary every day for one week before start of treatment and before evaluation of effect. Also, a quality of life form will be filled out before each consultation. In Part 2, the investigators will investigate long-term effect and safety of apixaban and reduce dose after 3 months to find the minimal effective dose. Part 2 includes participants from Part 1 study who experienced effect of treatment or who agree to continue apixaban treatment. Study start of Part 2 is at the end of Part 1. All participants receive the same dose of apixaban as in part 1 (5 mg twice daily), and after 3 months (visit 2) the dose is reduced to 2.5 mg twice daily.

Conditions

Venous Malformation, Low Flow; Anticoagulants

Keywords

apixaban; venous malformation; localized intravascular coagulation

Outcome Measures

Primary Outcomes (2)

• Difference between apixaban and placebo in change of self-reported pain intensity before and 8 weeks after starting treatment Change in type, dose and frequency of pain medication

  Average numeric rating scale (NRS) score(score 0-10 where 0 represents no pain and 10 represents worst imaginable pain) last 7 days before assessment

  From enrollment to the end of treatment at 8 and 17 weeks

• Change in pain medication

  Registration of type, dose and frequency of pain medication last 7 days before assessment

  From enrollment to the end of treatment at 8 and 17 weeks

Secondary Outcomes (5)

• Difference between apixaban and placebo in change of quality of life before and 8 weeks after starting treatment

  From enrollment until end of treatment, at 8 and 17 weeks

• Difference between apixaban and placebo in change of quality of life before and 8 weeks after starting treatment

  From enrollment until end of treatment, at 8 and 17 weeks]

• Difference between apixaban and placebo in change in coagulation parameters before and 8 weeks after

  From enrollment until after end of treatment at 8 and 17 weeks

• Change in pain intensity after 3 months treatment

  From enrollment of Part 2 until completion of treatment at 6 months

• Change in pain intensity three months after reducing dose

  At changing dose at 3 months after enrollment of Part 2 and after 6 months ( end of treatment)

Study Arms (2)

Apixaban

EXPERIMENTAL

Apixaban 5 mg twice daily

Drug: Apixaban (Eliquis)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Apixaban (Eliquis) DRUG

5 mg twice daily

Apixaban

Placebo DRUG

placebo twice daily

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Participant must be 18-85 years of age at the time of signing the informed consent form (ICF).
• \. Participants who have simple VM with LIC. VM must be diagnosed by MRi and LIC is defined as d-dimer \> 2 x upper reference area (21).
• \. Patients must experience pain from the malformation, NRS ≥4. Pain is defined as local pain in the malformation, and the participant must have pain that inhibits daily activity or pain during nighttime that interferes with sleep.

You may not qualify if:

• History of major bleeding, known disease of the GI tractus with risk of bleeding (ulcera, IBD, tumor), known hemostatic disorder/hemophilia, bariatric surgery or other condition resulting in impaired adsorption of drug, active cancer
• Lesion or condition if considered a significant risk factor for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities
• Current treatment with platelet inhibitor, any other anticoagulation treatment e.g. unfractionated heparin, low molecular weight heparin (dalteparin, enoxaparin), heparin derivates (fondaparinux), oral anticoagulants (warfarin, dabigatran, rivaroxaban, edoxaban), NSAIDs, cancer therapy with chemotherapy
• Current treatment with sirolimus
• Current treatment with azole-antimycotics (e.g., ketoconazole, itraconazole, voriconazole and posaconazole)
• Current treatment with HIV protease inhibitors (e.g., ritonavir)
• Weight \<50 kg
• Known hypersensitivity to the active substance or to any of the excipients listed in the SmPC.
• Impaired renal function (eGFR \< 50 ml/min)
• Impaired liver function, INR \> 1.3 or aminotransferases \> 3 times upper limit
• Pregnancy or breastfeeding
• Low platelet count (\<100 x 109/mL)
• Any condition that in the view of the investigator would suggest that the patient is unable to comply with the study protocol and procedures

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, 0372, Norway

Location

Related Publications (1)

• Liu H, Hu L, Yang X, Xu Z, Gu H, Chen H, Lin X. Dabigatran etexilate is efficacious in consumptive coagulopathy and pain associated with venous malformations. J Vasc Surg Venous Lymphat Disord. 2023 Mar;11(2):397-403.e1. doi: 10.1016/j.jvsv.2022.09.015. Epub 2022 Oct 31.

  PMID: 36328137 BACKGROUND

MeSH Terms

Interventions

apixaban

Central Study Contacts

Nina H Schultz, PhD MD

CONTACT

+4797636108; nischu@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study in which participants/care providers/investigators/outcomes assessors are blinded to study intervention.. In case of an emergency, the investigator has the responsibility for determining if unblinding of a participant's intervention assignment is warranted. Participant safety must always be the first consideration in making such a determination. The participant will be carrying a card with contact information of investigator and the medical monitor. The card will be in Norwegian and in English and inform that the person is part of a blinded trial and that he/she may be under anticoagulation with apixaban. In case of major bleeding, the investigator must be contacted who may unblind the participant so that emergency treatment can be considered. In case of a life-threatening bleed, there is no time for contacting the investigator. Then measures must be taken as if the participant is under anticoagulation treatment with apixaban
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Randomized study, crossover design, double-blind

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: December 11, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2031
• Last Updated: December 11, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)