Different Doses and Duration of Low Molecular Weight Heparin (Parnaparin)in Superficial Vein Thrombosis

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna (Other)

Overall Status

Completed

CT.gov ID

NCT00362947

Collaborator

(none)

664

Enrollment

Locations

Arms

Duration (Months)

332

Patients Per Site

6.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The optimal treatment of superficial venous thrombosis (SVT) is still uncertain. Though low molecular weight heparin (LMWH) is considered the treatment of choice, studies conducted so far do not give clear indications of the optimal dose and duration of treatment. This study aims to evaluate whether an intermediate therapeutic dose of LMWH (parnaparin) is more effective than a prophylactic dose and also to assess whether 10 rather than 30 days are sufficient for treatment.

Condition or Disease	Intervention/Treatment	Phase
Thrombophlebitis	Drug: LMWH parnaparin subcutaneously	Phase 3

Detailed Description

Outpatients with an episode of SVT of the grand saphenous vein (for at least 4 cm), and/or SVT of the small saphenous vein (for at least 4 cm), and/or SVT of a collateral vein of the large saphenous vein of the thigh (for at least 4cm) are included in this prospective, randomised, double blind, national multicentre study.

Patients will be randomised into double-blind groups to receive (syringes will be identical in appearance) in consecutively numbered boxes:

A - Parnaparin, dose of 8,500 IU aXa taken subcutaneously once a day for 10 days B - Parnaparin, dose of 8,500 IU aXa per day for 10 days followed by Parnaparin 6,400 IU aXa per day for the subsequent three weeks. C - Parnaparin, dose of 4,250 IU aXa per day for 30 days Elastic compression treatment will be recommended with special stocking and/or elastic bandaging with compression to the ankles of 20-40 mmHg, where not contraindicated.

Study Design

Study Type:

Interventional

Actual Enrollment :

664 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomized Clinical Study of Different Treatment Doses and Duration of Low Molecular Weight Heparin (Parnaparin) in Superficial Vein Thrombosis

Study Start Date :

Aug 1, 2006

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: A A - Parnaparin 8.500 UI aXa od (therapeutic doses) for 10 days followed by placebo for 20 days	Drug: LMWH parnaparin subcutaneously
Active Comparator: B B - Parnaparin 8.500 UI aXa od for 10 days followed by 6.400 UI aXa once daily (intermediate therapeutic doses) for 20 days	Drug: LMWH parnaparin subcutaneously
Active Comparator: C C - Parnaparin 4.250 UI aXa od (prophylactic doses) for 30 days	Drug: LMWH parnaparin subcutaneously

Arm

Intervention/Treatment

Placebo Comparator: A

A - Parnaparin 8.500 UI aXa od (therapeutic doses) for 10 days followed by placebo for 20 days

Drug: LMWH parnaparin subcutaneously

Active Comparator: B

B - Parnaparin 8.500 UI aXa od for 10 days followed by 6.400 UI aXa once daily (intermediate therapeutic doses) for 20 days

Drug: LMWH parnaparin subcutaneously

Active Comparator: C

C - Parnaparin 4.250 UI aXa od (prophylactic doses) for 30 days

Drug: LMWH parnaparin subcutaneously

Outcome Measures

Primary Outcome Measures

Primary effectiveness objectives [33 days]
composite of symptomatic and asymptomatic DVT, relapse and/or symptomatic or asymptomatic local extension of SVT and symptomatic PE at 33 days.
Major bleeding [33]
Bleeding events were defined as major if retroperitoneal, intracranial, intraocular with severe vision damage, intra-articular, intra-abdominal of upper or lower digestive tract, genito-urinary tract, respiratory tract or associated with a decrease in the haemoglobin of ≥ 2.0 g/dL, or if requiring transfusion of ≥2 units of blood or if fatal. Bleeding was classified as minor in all other cases.

Secondary Outcome Measures

Secondary effectiveness objectives [93]
i)- reduction in local symptoms during treatment and ii)- the combined efficacy end-point during a follow-up of 93 days after the start of treatment.
secondary outcome for safety [33]
the composite of minor haemorrhages, thrombocytopenia or any other adverse events (e.g. local allergic reactions).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Weight > 50 kg and less than 110 kg
SVT of the grand saphenous vein for at least 4 cm
SVT of the small saphenous vein for at least 4 cm
Collateral SVT of the large saphenous vein of the thigh for at least 4cm

Exclusion Criteria:

SVT of the grand saphenous vein reaching the saphenofemoral cross (within 3 cm)
SVT of the small saphenous vein reaching the saphenopopliteal cross
Documented proximal or distal DVT or pulmonary embolism
SVT secondary to sclerotherapy
Pregnancy and puerperium
uncontrolled arterial hypertension (Systolic pressure > 180 mmHg and diastolic pressure > 110 mmHg)
Active peptic ulcer
Bacterial endocarditis
Stroke in the previous 3 months
Haemorrhagic diathesis
Thrombocytopenia (platelets < 100,000/ µL)
Hypersensitivity to heparin or history of thrombocytopenia induced by heparin
Creatinine > 2 mg% (> 180 µmol/L)
Heparin therapy (any dose) or anticoagulant therapy for longer than the previous 72 hours
In-hospital development of SVT
Previous saphenectomy by any method
Surgery in the previous 30 days
Serious liver disease
Use of dextran, mannitol, thrombolytic treatment, chronic use of NSAID and cortisone-based drugs.
Active cancer or under chemotherapy or radiotherapy
Thrombectomy of superficial vein involved
Refusal to give informed consent