Innohep® in Elderly Patients With Impaired Renal Function Treated for Acute Deep Vein Thrombosis

Safety Profile of Innohep Versus Subcutaneous Unfractionated Heparin in Elderly Patients With Impaired Renal Function Treated for Acute Deep Vein Thrombosis

The objective of the study is to compare the safety of innohep® and Unfractionated Heparin (UFH) in terms of clinically relevant bleedings in elderly patients with impaired renal function for initial treatment of acute Deep Venous Thrombosis (DVT).

The primary response criterion is the percentage of patients with clinically relevant bleeding events prior to day 90 +/- 5.

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis
• Intervention / Treatment: Drug: innohep®; Drug: Heparin

• Study Type: Interventional
• Enrollment (Actual): 541
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Bulgaria - managed by CRO
• Croatia
  • Zagreb, Croatia
    • Croatia - managed by CRO
• Czechia
  • Praha, Czechia
    • Czech Republic - managed by CRO
• France
  • Brest, France, 29609
    • Hopital De La Cavale Blanche
• Germany
  • Darmstadt, Germany, 64297
    • Med. Klinik IV/Klinikum Darmstadt
• Poland
  • Szczecin, Poland, 70-111
    • Klinika Chirugii Naczyniowej
• Romania
  • Bucharest, Romania, 010965
    • Romania - managed by CRO
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center Serbia, Institute of Cardiovascular diseases & Centre for Vascular Surgery-Belgrade
• Spain
  • Madrid, Spain, 28040
    • Service of Geriatry, Hospital Universitario Clínico San Carlos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 68 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a symptomatic and objectively confirmed Venous Thromboembolism (VTE) (lower limb deep venous thrombosis (DVT) or pulmonary embolus (PE)) with mandatory presences of objectively confirmed and treatment requiring DVT, i.e. symptomatic and objectively confirmed distal DVT or objectively confirmed, symptomatic or asymptomatic proximal DVT (confirmation of DVT should be performed by ultrasonography or venography within 48 hous prior to randomisation)
• Patients with an indication for DVT treatment with SC Low Molecular Weight Heparin (LMWH) or Unfractionated Heparin (UFH) followed by Oral Anticoagulant (OAC) for at least 90 days
• Hospitalized patients who, during SC anticoagulant treatment, will be followed, as specified in the protocol, on a daily basis either in the hospital or in an out-patient setting
• Patients at or above 75 years with a creatinine clearance less than or equal to 60 mL/min calculated according to the Cockcroft-Gault formula
• Patients at or above 70 years with a creatinine clearance less than or equal to 30 mL/min calculated according to the Cockcroft-Gault formula

Exclusion Criteria:

• Patients receiving high dose (i.e. equivalent to a dose recommended for treatment of DVT) of UFH or LMWH or thrombolytic agents within the last 4 weeks except for UFH/LMWH during the last 36 hours prior to randomisation
• Patients on oral anticoagulant treatment (vitamin K-antagonists) at or within last 1 week prior to randomisation
• Patients with a symptomatic venous thromboembolism (VTE) requiring thrombolytic therapy or invasive intervention
• End stage renal disease patients requiring dialysis
• Surgery within 2 weeks prior to randomisation or planned surgery, epidural anaesthesia and/or spinal anaesthesia during the SC anticoagulant treatment period
• Planned use of acetylsalicylic acid in doses above 300 mg/day, NSAID or Dextran 40 at randomisation and during the SC anticoagulant treatment period
• Patients with a current overt bleeding or known haemorrhage condition (e.g. active G.I. ulcer)
• Patients with a platelet count < 100 x 10 9/L
• Patients with a known history of heparin-induced thrombocytopenia
• Patients with known severe hepatic insufficiency manifested as international normalized ratio (INR) greater than or equal to 1.5
• Patients with uncontrolled severe hypertension i.e. a systolic blood pressure > 220 mm Hg or diastolic blood pressure > 120 mm Hg during at least 2 measurements within 24 hours prior to randomisation
• Patients with ischaemic stroke at or within last 1 week prior to randomisation
• Patients with a known haemorrhagic stroke within 3 months prior to randomisation
• Patients with known bacterial endocarditis within 3 months prior to randomisation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: innohep®; innohep® 175 anti-Xa IU/kg once daily	Drug: innohep®; 175 anti-Xa IU/kg administered subcutaneously (SC) once daily
Active Comparator: Heparin; Heparin 50 IU /kg followed by a total dose of 400 to 600 IU/kg/day divided into two SC injections daily.	Drug: Heparin; Heparin 50 IU /kg followed by a total dose of 400 to 600 IU/kg/day divided into two SC injections daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Clinically Relevant Bleeding Events	prior to day 90 +/- 5

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Recurrence of Venous Thromboembolism	prior to day 90 +/- 5
Number of Patients With Major Bleeding Events	prior to day 90 +/- 5

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Principal Investigator: Alain Leizorovicz, MD, Faculté de Médecine Laënnec

Publications and helpful links

General Publications

• Leizorovicz A, Siguret V, Mottier D; Innohep(R) in Renal Insufficiency Study Steering Committee, Leizorovicz A, Siguret V, Mottier D, Clonier F, Janas M, Stinson J, Townshend G, Maddalena M. Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep(R) in Renal Insufficiency Study (IRIS). Thromb Res. 2011 Jul;128(1):27-34. doi: 10.1016/j.thromres.2011.03.002. Epub 2011 Apr 7.

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: January 13, 2006
• First Submitted That Met QC Criteria: January 13, 2006
• First Posted (Estimate): January 16, 2006

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: February 27, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Acute, symptomatic and objectively confirmed DVT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Embolism and Thrombosis; Renal Insufficiency; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Tinzaparin
• Other Study ID Numbers: IN 0401 INT