Superficial ThrombophlebitisPhase 4REVETRNCT01245998
Efficacy of Low Molecular Weight Heparin in Superficial Vein Thrombosis
A Phase 4 study testing Dalteparin in people with Superficial Thrombophlebitis, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
The aim of the study is to establish whether treatment of superficial vein thrombosis (SVT) with low-molecular-weight heparin in preventive or therapeutic doses prevents disease progression and thromboembolic events (deep vein thrombosis and pulmonary embolism), whether efficacy of low-molecular-weight heparin differs… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Superficial Thrombophlebitis
- What is being tested?
- Dalteparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteSlovenia
- Study dates
- 1 Dec 2010to 1 Jan 2014
- Phase
- Phase 4
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- written informed consent to participate in the study
- symptomatic thrombophlebitis of the great saphenous vein measuring at least 10 cm or the small saphenous vein measuring at least 10 cm or a collateral of the great saphenous vein measuring at least 10 cm (within 7 days from the onset of the disease)
- age 18 to 85 years
- body weight 65 to 85 kg
Who cannot join
- inability to objectively confirm the diagnosis
- excessive or insufficient body weight (more than 85 kg or less than 60 kg)
- history of previous thromboembolic complications (including previous thrombophlebitis, vein thrombosis and pulmonary embolism)
- contraindications for anticoagulant treatment
- active bleeding or high risk for bleeding contraindicating treatment with (LMWH)
- diseases requiring anticoagulant treatment
Show all 13Show fewer
- proximal or distal deep vein thrombosis or pulmonary embolism (either symptomatic or incidentally found asymptomatic)
- thrombophlebitis of the great saphenous vein at a distance of less than 5 cm from the saphenofemoral junction or thrombophlebitis of small saphenous vein at a distance of less than 3 cm from the saphenopopliteal junction
- thrombophlebitis that might arise as a consequence of a previous intravenous access (infusion thrombophlebitis), sclerotherapy or surgical treatment of chronic vein insufficiency
- pregnancy, known malignant disease or chemotherapy
- immobility
- advanced stage of kidney failure (GF < 30 mL/min/1.72 m2)
- significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis) or alanine transaminase (ALT) >\= 2 times the upper limit of normal (ULN), or total bilirubin (TBL) x 1.5 times the ULN
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective, Randomized, Double-blinded Trial of the Efficacy and Safety of Different Doses and Duration of Low Molecular Weight Heparin (Dalteparin) in Superficial Vein Thrombosis
The aim of the study is to establish whether treatment of superficial vein thrombosis (SVT) with low-molecular-weight heparin in preventive or therapeutic doses prevents disease progression and thromboembolic events (deep vein thrombosis and pulmonary embolism), whether efficacy of low-molecular-weight heparin differs with regard to the dosage used (prevention, treatment), and to recognize groups of patients in which treatment with heparin is most efficient, as well as to determine factors that influence the efficacy of SVT treatment with heparin.
Read the detailed description
Until recently thrombophlebitis was regarded as a benign and self-limiting disease. Recent studies have shown that various complications, especially vein thrombosis and pulmonary thromboembolism, often accompany SVT. An observational study (Prospective Observational Superficial Thrombophlebitis - POST) showed that three months after onset of the disease thromboembolic events occurred in 10% of patients: pulmonary embolism in 0.4%, disease progression in 3.1% and disease recurrence in 1.9% of patients. Therefore, SVT is now frequently regarded as a part of the thromboembolic syndrome. On the basis of the evidence referred to above anticoagulants, especially heparin, are used more and more often for treatment of SVT instead of anti-inflammatory drugs and non-steroidal antirheumatics. Several studies performed so far have examined the efficacy of standard and low-molecular-weight heparin in various doses, but no final conclusion on the efficacy of treatment of SVT with heparin has been established yet.
A study by Marchiori and colleagues showed that 8-12-day treatment of SVT with preventive and therapeutic doses of low-molecular-weight heparin significantly reduces progression and relapse of the disease, but not its thromboembolic complications. Another study demonstrated that low-molecular-weight heparin in combination with elastic compression was not significantly more effective than compression alone. Comparison of preventive and therapeutic doses of low-molecular-weight heparin given to patients over the period of one month after disease onset showed no differences in the efficacy in prevention of disease progression and thromboembolic complications. The standard (unfractionated) heparin was also shown to be effective in preventing disease progression, however, but not in preventing thromboembolic complications. It is also not clear how long the treatment with heparin should last. So far only one study compared the efficacy of treatment with various doses of low-molecular-weight heparin from one month to three months' duration; it demonstrated that 1-month treatment with lower doses of heparin was as effective as 3-month treatment with therapeutic doses of heparin. A recent study (CALISTO) compared the efficacy of preventive doses of fondaparinux (2.5 mg) with placebo in more than 3,000 patients with SVT and concluded that anticoagulant treatment of SVT probably does not significantly influence prevention of thromboembolic complications (Abstract presented at the 5th Annual Meeting of the American Society of Hematology).
Results of recent studies show that heparin (standard or low-molecular-weight heparin) in various doses prevents SVT progression, but no final agreement has emerged as to whether they prevent the occurrence of thromboembolic complications. Interpretation of the results is difficult because of the heterogeneity of the patients included in certain studies and especially because of unavailability of subgroup analyses, which would help to establish whether treatment with heparin is more effective in certain groups of patients with SVT than in those with presenting forms of the disease. Latest (2008) guidelines for prevention of venous thromboembolic events adopted by the American College of Chest Physicians (ACCP) recommend treatment with at least preventive or median doses of low-molecular-weight heparin or standard heparin for the duration of not less than 4 weeks. This recommendation was based on a very low evidence level (level 2B).
In this study, we aim to investigate whether the extensiveness of thrombophlebitis and the proximal distance of the end of a blood clot from saphenofemoral and saphenopopliteal junction influence the efficacy of SVT treatment with heparin. The investigators shall also monitor the expression of systemic inflammatory parameters that might be related to the efficacy of the treatment and progression of the disease.
- Conditions
- Superficial Thrombophlebitis
- Being tested
- Dalteparin
- Keywords
- Thrombophlebitis, Venous thrombosis, Pulmonary embolism, Anticoagulants, Low-Molecular-Weight Heparin
- Medical subject headings
- Thrombophlebitis, Venous Thrombosis, Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DalteparinDrug
Also called Fragmin
dalteparin 5000 I.U./24 h s.c. for 6 weeks
DalteparinDrug
Also called Fragmin
dalteparin 15000 I.U./24 h s.c. for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| dalteparin 5000 I.U./24 h s.c. | Active comparator | Not described Receives: Drug: Dalteparin |
| dalteparin 15000 I.U./24 h s.c. | Active comparator | Not described Receives: Drug: Dalteparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the efficacy and safety of low-molecular-weight heparin - dalteparin in patients with ST
To compare the efficacy of therapeutic vs. preventive doses of dalteparin in prevention of thromboembolic complications and disease progression in patients with acute thrombophlebitis of lower extremities
Measured: 3 months
Combined end-point: occurrence of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism or ultrasonographic blood clot progression or relapse of ST
Measured: 3 months
Clinically relevant bleeding occurring
(i.e., major or clinically relevant non-major bleeding)
Measured: during treatment
Secondary outcomes (4)
To investigate the safety of ST treatment with preventive doses of dalteparin compared with therapeutic doses, death, bleeding, heparin-induced thrombocytopenia (HIT)
Measured: 3 months
To ascertain whether the extent or progression of ST is related to systemic inflammatory parameters
Measured: 12 months
To study a possible correlation between effectiveness of treatment of ST with preventive and therapeutic doses of dalteparin and severity of systemic inflammatory parameters.
Measured: 12 months
To determine whether the extension of anticoagulant treatment with the study drug for additional six weeks is more effective and safer
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2010 (estimated)
- Study start1 Dec 2010
- Primary completion3 Dec 2012
- Study completion1 Jan 2014
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 Superficial ThrombophlebitisStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pavel POREDOS, University Medical Centre Ljubljana
- Investigators
- Pavel Poredos, M.D., Ph.D., Principal investigator, University Medical Centre Ljubljana, Department of Vascular Disease
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01245998
- Sponsor's protocol ID
- REVETR2010
- Acronym
- REVETR
- Status last verified
- May 2018
- First submitted
- 22 Nov 2010
- Last updated
- 4 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Spirkoska A, Jezovnik MK, Poredos P. Time course and the recanalization rate of superficial vein thrombosis treated with low-molecular-weight heparin. Angiology. 2015 Apr;66(4):381-6. doi: 10.1177/0003319714533183. Epub 2014 May 7.
PubMed 24807875
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Double-blinded Trial of the Efficacy and Safety of Different Doses and Duration of Low Molecular Weight Heparin (Dalteparin) in Superficial Vein Thrombosis
- ClinicalTrials.gov ID
- NCT01245998
- Acronym / sponsor ID
- REVETR / REVETR2010
- Conditions
- Superficial Thrombophlebitis
- Keywords
- Thrombophlebitis, Venous thrombosis, Pulmonary embolism, Anticoagulants, Low-Molecular-Weight Heparin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- 1 Dec 2010 (actual)
- Primary completion
- 3 Dec 2012 (actual)
- Study completion
- 1 Jan 2014 (actual)
- First posted
- 23 Nov 2010 (estimated)
- 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.
The aim of the study is to establish whether treatment of superficial vein thrombosis (SVT) with low-molecular-weight heparin in preventive or therapeutic doses prevents disease progression and thromboembolic events (deep vein thrombosis and pulmonary embolism), whether efficacy of low-molecular-weight heparin differs with regard to the dosage used (prevention, treatment), and to recognize groups of patients in which treatment with heparin is most efficient, as well as to determine factors that influence the efficacy of SVT treatment with heparin.
Detailed description
Until recently thrombophlebitis was regarded as a benign and self-limiting disease. Recent studies have shown that various complications, especially vein thrombosis and pulmonary thromboembolism, often accompany SVT. An observational study (Prospective Observational Superficial Thrombophlebitis - POST) showed that three months after onset of the disease thromboembolic events occurred in 10% of patients: pulmonary embolism in 0.4%, disease progression in 3.1% and disease recurrence in 1.9% of patients. Therefore, SVT is now frequently regarded as a part of the thromboembolic syndrome. On the basis of the evidence referred to above anticoagulants, especially heparin, are used more and more often for treatment of SVT instead of anti-inflammatory drugs and non-steroidal antirheumatics. Several studies performed so far have examined the efficacy of standard and low-molecular-weight heparin in various doses, but no final conclusion on the efficacy of treatment of SVT with heparin has been established yet.
A study by Marchiori and colleagues showed that 8-12-day treatment of SVT with preventive and therapeutic doses of low-molecular-weight heparin significantly reduces progression and relapse of the disease, but not its thromboembolic complications. Another study demonstrated that low-molecular-weight heparin in combination with elastic compression was not significantly more effective than compression alone. Comparison of preventive and therapeutic doses of low-molecular-weight heparin given to patients over the period of one month after disease onset showed no differences in the efficacy in prevention of disease progression and thromboembolic complications. The standard (unfractionated) heparin was also shown to be effective in preventing disease progression, however, but not in preventing thromboembolic complications. It is also not clear how long the treatment with heparin should last. So far only one study compared the efficacy of treatment with various doses of low-molecular-weight heparin from one month to three months' duration; it demonstrated that 1-month treatment with lower doses of heparin was as effective as 3-month treatment with therapeutic doses of heparin. A recent study (CALISTO) compared the efficacy of preventive doses of fondaparinux (2.5 mg) with placebo in more than 3,000 patients with SVT and concluded that anticoagulant treatment of SVT probably does not significantly influence prevention of thromboembolic complications (Abstract presented at the 5th Annual Meeting of the American Society of Hematology).
Results of recent studies show that heparin (standard or low-molecular-weight heparin) in various doses prevents SVT progression, but no final agreement has emerged as to whether they prevent the occurrence of thromboembolic complications. Interpretation of the results is difficult because of the heterogeneity of the patients included in certain studies and especially because of unavailability of subgroup analyses, which would help to establish whether treatment with heparin is more effective in certain groups of patients with SVT than in those with presenting forms of the disease. Latest (2008) guidelines for prevention of venous thromboembolic events adopted by the American College of Chest Physicians (ACCP) recommend treatment with at least preventive or median doses of low-molecular-weight heparin or standard heparin for the duration of not less than 4 weeks. This recommendation was based on a very low evidence level (level 2B).
In this study, we aim to investigate whether the extensiveness of thrombophlebitis and the proximal distance of the end of a blood clot from saphenofemoral and saphenopopliteal junction influence the efficacy of SVT treatment with heparin. The investigators shall also monitor the expression of systemic inflammatory parameters that might be related to the efficacy of the treatment and progression of the disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dalteparin 5000 I.U./24 h s.c. | Active comparator | Drug: Dalteparin |
| dalteparin 15000 I.U./24 h s.c. | Active comparator | Drug: Dalteparin |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- written informed consent to participate in the study
- symptomatic thrombophlebitis of the great saphenous vein measuring at least 10 cm or the small saphenous vein measuring at least 10 cm or a collateral of the great saphenous vein measuring at least 10 cm (within 7 days from the onset of the disease)
- age 18 to 85 years
- body weight 65 to 85 kg
Key exclusion criteria (13 listed)
- inability to objectively confirm the diagnosis
- excessive or insufficient body weight (more than 85 kg or less than 60 kg)
- history of previous thromboembolic complications (including previous thrombophlebitis, vein thrombosis and pulmonary embolism)
- contraindications for anticoagulant treatment
- active bleeding or high risk for bleeding contraindicating treatment with (LMWH)
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 |
|---|---|---|
| DalteparinAlso: Fragmindalteparin 5000 I.U./24 h s.c. for 6 weeks | Drug | dalteparin 5000 I.U./24 h s.c. |
| DalteparinAlso: Fragmindalteparin 15000 I.U./24 h s.c. for 6 weeks | Drug | dalteparin 15000 I.U./24 h s.c. |
Primary outcome
To assess the efficacy and safety of low-molecular-weight heparin - dalteparin in patients with ST
Time frame: 3 months
To compare the efficacy of therapeutic vs. preventive doses of dalteparin in prevention of thromboembolic complications and disease progression in patients with acute thrombophlebitis of lower extremities
Combined end-point: occurrence of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism or ultrasonographic blood clot progression or relapse of ST
Time frame: 3 months
Clinically relevant bleeding occurring
Time frame: during treatment
(i.e., major or clinically relevant non-major bleeding)
4 secondary outcomes
To investigate the safety of ST treatment with preventive doses of dalteparin compared with therapeutic doses, death, bleeding, heparin-induced thrombocytopenia (HIT)
Time frame: 3 months
To ascertain whether the extent or progression of ST is related to systemic inflammatory parameters
Time frame: 12 months
To study a possible correlation between effectiveness of treatment of ST with preventive and therapeutic doses of dalteparin and severity of systemic inflammatory parameters.
Time frame: 12 months
To determine whether the extension of anticoagulant treatment with the study drug for additional six weeks is more effective and safer
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2018.
- Results publication: PubMed 24807875Spirkoska A, Jezovnik MK, Poredos P. Time course and the recanalization rate of superficial vein thrombosis treated with low-molecular-weight heparin. Angiology. 2015 Apr;66(4):381-6. doi: 10.1177/0003319714533183. Epub 2014 May 7.
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. This study is not recruiting at the moment.
Pavel Poredos, M.D., Ph.D. principal investigator
University Medical Centre Ljubljana, Department of Vascular Disease
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dalteparin in people with Superficial Thrombophlebitis, run by University Medical Centre Ljubljana at 1 site in Slovenia.
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: finished, as of the sponsor's last update on 4 May 2018. 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 Slovenia. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess the efficacy and safety of low-molecular-weight heparin - dalteparin in patients with ST (time frame: 3 months). The study lists 3 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 NCT01245998, 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 4 May 2018.