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

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

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.

Study Overview

• Status: Completed
• Conditions: Thrombophlebitis
• Intervention / Treatment: Drug: LMWH parnaparin subcutaneously

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 Type: Interventional
• Enrollment (Actual): 664
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Dept. Angiology & Blood Coagulation; University Hospital S.Orsola-Malpighi
  • PC
    • Piacenza, PC, Italy, 29100
      • U.O. Medicina Critica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary effectiveness objectives	composite of symptomatic and asymptomatic DVT, relapse and/or symptomatic or asymptomatic local extension of SVT and symptomatic PE at 33 days.	33 days
Major bleeding	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.	33

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary effectiveness objectives	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.	93
secondary outcome for safety	the composite of minor haemorrhages, thrombocytopenia or any other adverse events (e.g. local allergic reactions).	33

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Benilde Cosmi, MD PhD, University of Bologna

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (ACTUAL): September 1, 2010
• Study Completion (ACTUAL): February 1, 2011

Study Registration Dates

• First Submitted: August 11, 2006
• First Submitted That Met QC Criteria: August 11, 2006
• First Posted (ESTIMATE): August 15, 2006

Study Record Updates

• Last Update Posted (ACTUAL): March 19, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: thrombophlebitis; LMWH; Superficial vein thrombosis; parnaparin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Vasculitis; Peripheral Vascular Diseases; Phlebitis; Thrombosis; Venous Thrombosis; Thrombophlebitis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Parnaparin
• Other Study ID Numbers: The Steflux study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO