Venous Malformation, Low FlowPhase 2AVANCT06729034
A Study of Direct Oral Anticoagulants in Patients with Painful Venous Malformations with Localized Intravascular Coagulation
A Phase 2 study testing Apixaban (Eliquis) in people with Venous Malformation, Low Flow and Anticoagulants, run by Oslo University Hospital at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Venous Malformation, Low Flow, Anticoagulants
- What is being tested?
- Apixaban (Eliquis)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteNorway
- Study dates
- 1 Feb 2025to 31 Dec 2031
- Phase
- Phase 2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Participant must be 18-85 years of age at the time of signing the informed consent form (ICF).
- 2. 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).
- 3. 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.
- 4. Body weight over 50 kg. 5. Pregnancy test at time of inclusion must be negative 6. Capable of giving written informed consent
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Norway1 site
Oslo University Hospital
Oslo, 0372
Nina H Schultz, MD PhD, +47 97636108, nischu@ous-hf.no
Puneet Kaur, MD, +47 45460140, puneet.kaur@lds.no
About this study
Official title: A Single-center Blinded Crossover Study Investigating the Efficacy of Apixaban in Patients with Painful Venous Malformations with Localized Intravascular Coagulation
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.
Read more
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.
Read the detailed description
There are no established universal guidelines on the hematologic management of patients with venous malformations (VM) with and without localized intravascular coagulopathy (LIC). Anticoagulation treatment with low molecular weight heparin (LMWH) has improved functionality and decreased pain in patients with VM with localized LIC.
The aim is to study the effect of the direct oral anticoagulant apixaban in patients with painful venous malformations with localized intravascular coagulation.
Apixaban is an oral direct acting anticoagulant shown to be as effective and safe as LMWH and warfarin in treating venous thrombosis.
single-center, prospective double-blind crossover superiority study including patients with venous malformations at age 18-85 years. The participants are randomized to different treatment orders of the two treatment periods with apixaban and placebo. Masking of participants and study personell. Randomization at screening to arm 1 or arm 2. 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 one week.
Part 2: The AVA Long study is an open-label observational study including participants from the AVA study who experienced effect of treatment or who agree to continue apixaban treatment. Study start of AVA long (part 2) is at study end of part 1. The participants receive the dose of apixaban as in part 1 (5 mg twice daily), but open-label, and after 3 months (visit 2) the dose is reduced to 2.5 mg twice daily. The investigators will investigate long-term efficacy and safety of apixaban and find the minimal effective dose.
- Conditions
- Venous Malformation, Low Flow, Anticoagulants
- Being tested
- Apixaban (Eliquis), Placebo
- Keywords
- apixaban, venous malformation, localized intravascular coagulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apixaban (Eliquis)Drug
5 mg twice daily
PlaceboDrug
placebo twice daily
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Experimental | Apixaban 5 mg twice daily Receives: Drug: Apixaban (Eliquis) |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Outcome Measure for Vascular Malformation (OVAMA) questionnaire
Measured: 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
Short form survey-36 (SF-36)
Measured: 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
D-dimer
Measured: From enrollment until after end of treatment at 8 and 17 weeks
Change in pain intensity after 3 months treatment
Numeric rating scale (NRS) score at time of evaluation (score 0-10 where 0 represents no pain and 10 represents worst imaginable pain)
Measured: From enrollment of Part 2 until completion of treatment at 6 months
Change in pain intensity three months after reducing dose
Numeric rating scale (NRS) score at time of evaluation (score 0-10 where 0 represents no pain and 10 represents worst imaginable pain)
Measured: At changing dose at 3 months after enrollment of Part 2 and after 6 months ( end of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2024
- Study start1 Feb 2025 (estimated)
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2031 (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 Venous Malformation, Low FlowStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized study, crossover design, double-blind
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nina Haagenrud Schultz, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06729034
- Sponsor's protocol ID
- 2024-511930-11-00
- Other IDs
- 2024-511930-11-00
- Acronym
- AVA
- Status last verified
- Oct 2024
- First submitted
- 30 Oct 2024
- Last updated
- 11 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data protection regulations does not allow sharing individual participant data
Publications
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.
PubMed 36328137
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center Blinded Crossover Study Investigating the Efficacy of Apixaban in Patients with Painful Venous Malformations with Localized Intravascular Coagulation
- ClinicalTrials.gov ID
- NCT06729034
- Acronym / sponsor ID
- AVA / 2024-511930-11-00
- Conditions
- Venous Malformation, Low Flow, Anticoagulants
- Keywords
- apixaban, venous malformation, localized intravascular coagulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 1 Feb 2025 (estimated)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 11 Dec 2024 (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.
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.
Detailed description
There are no established universal guidelines on the hematologic management of patients with venous malformations (VM) with and without localized intravascular coagulopathy (LIC). Anticoagulation treatment with low molecular weight heparin (LMWH) has improved functionality and decreased pain in patients with VM with localized LIC.
The aim is to study the effect of the direct oral anticoagulant apixaban in patients with painful venous malformations with localized intravascular coagulation.
Apixaban is an oral direct acting anticoagulant shown to be as effective and safe as LMWH and warfarin in treating venous thrombosis.
single-center, prospective double-blind crossover superiority study including patients with venous malformations at age 18-85 years. The participants are randomized to different treatment orders of the two treatment periods with apixaban and placebo. Masking of participants and study personell. Randomization at screening to arm 1 or arm 2. 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 one week.
Part 2: The AVA Long study is an open-label observational study including participants from the AVA study who experienced effect of treatment or who agree to continue apixaban treatment. Study start of AVA long (part 2) is at study end of part 1. The participants receive the dose of apixaban as in part 1 (5 mg twice daily), but open-label, and after 3 months (visit 2) the dose is reduced to 2.5 mg twice daily. The investigators will investigate long-term efficacy and safety of apixaban and find the minimal effective dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized study, crossover design, double-blind
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Experimental | Drug: Apixaban (Eliquis)Apixaban 5 mg twice daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 1. Participant must be 18-85 years of age at the time of signing the informed consent form (ICF).
- 2. 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).
- 3. 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.
- 4. Body weight over 50 kg. 5. Pregnancy test at time of inclusion must be negative 6. Capable of giving written informed consent
Key exclusion criteria (13 listed)
- 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)
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 |
|---|---|---|
| Apixaban (Eliquis)5 mg twice daily | Drug | Apixaban |
| Placeboplacebo twice daily | Drug | Placebo |
Primary outcome
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
Time frame: From enrollment to the end of treatment at 8 and 17 weeks
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
Change in pain medication
Time frame: From enrollment to the end of treatment at 8 and 17 weeks
Registration of type, dose and frequency of pain medication last 7 days before assessment
5 secondary outcomes
Difference between apixaban and placebo in change of quality of life before and 8 weeks after starting treatment
Time frame: 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
Time frame: 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
Time frame: From enrollment until after end of treatment at 8 and 17 weeks
Change in pain intensity after 3 months treatment
Time frame: From enrollment of Part 2 until completion of treatment at 6 months
Change in pain intensity three months after reducing dose
Time frame: At changing dose at 3 months after enrollment of Part 2 and after 6 months ( end of treatment)
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 11 Dec 2024.
- Background: PubMed 36328137Liu 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.
- Individual participant dataSharing planned: No. Data protection regulations does not allow sharing individual participant data
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apixaban (Eliquis) in people with Venous Malformation, Low Flow and Anticoagulants, run by Oslo University Hospital at 1 site in Norway.
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 4 inclusion and 13 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: opening soon, as of the sponsor's last update on 11 Dec 2024. 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 Norway. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Nina H Schultz, PhD MD (+4797636108, nischu@ous-hf.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: From enrollment to the end of treatment at 8 and 17 weeks). The study lists 2 primary outcomes in all. 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 NCT06729034, 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 11 Dec 2024.