Study Comparing Desirudin With Heparin to Prevent Vein Clots After Heart and Lung Surgery

NCT00329433 | Completed Phase 2 Results DMC

• 1 other identifier: 05-0969
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

A blood clot in the veins, also known as deep venous thrombosis (DVT), is one of the most common complications after surgery. This may result in death if a clot breaks off and travel to the lungs; this is referred to as pulmonary embolism (PE). After heart surgery the incidence of DVT ranges from 20-48% and following lung surgery the incidence is 19-26%. In order to decrease the likelihood of this complication, patients receive by injection a blood thinning medicine. Heparin is the usual medicine used for this purpose following heart and lung surgery. Recently there have been reports that other medicines may be more effective than heparin for this purpose. Also there have been reports that some patients develop antibodies to heparin. When this occurs, this may prevent the heparin from being effective and may even promote the formation of blood clots. Antibodies to heparin may be present more often following heart and lung surgery than other types of surgery. There is a new medicine called desirudin (Iprivask), which may be used instead of heparin to prevent blood clots following heart and lung surgery. Desirudin is currently approved by the FDA to prevent blood clots following hip surgery. The purpose of this study is to compare desirudin with heparin for the prevention of vein clots after heart and lung surgery.

Conditions

Deep Venous Thrombosis

Keywords

Deep venous thrombosis; DVT; Heparin induced thrombocytopenia; HIT; Direct thrombin inhibitor

Outcome Measures

Primary Outcomes (1)

• The Primary Outcome Measure Was the Number of Participants With New Heparin Platelet Factor 4 (HIT Positive) Antibodies in Each Group Within 30 Days Following Surgery.

  Blood samples were collected and tested in singlet for the presence of PF4/heparin antibodies. Samples were collected for each participant on PDD (Post-study Drug initiation Day) 2, PDD 7 or at hospital discharge, and at 30 days post surgery.

  30 days after surgery

Secondary Outcomes (2)

• The Incidence of DVTs in Each Group.

  7 days after surgery

• The Incidence of Bleeding in Each Group.

  Up to 30 days after surgery

Study Arms (2)

Heparin

ACTIVE COMPARATOR

Both groups of patients will receive study drug three times a day (TID) for DVT prophylaxis. The current TID schedule is 0900, 1300, and 2100. The patients who are randomized to the Heparin (standard of care) group will receive subcutaneous injections of heparin three times a day (0900, 1300 and 2100).

Drug: Heparin

Desirudin (Iprivask™)

EXPERIMENTAL

Both groups of patients will receive study drug three times a day (TID) for DVT prophylaxis. The current TID schedule is 0900, 1300, and 2100. Patients who are randomized to the desirudin (study) group will receive 15 mg of subcutaneous desirudin twice a day (at 0900 and 2100). These patients will also receive an injection of normal saline placebo at 1300 so that patients in both groups will receive three injections at the same time points.

Drug: Desirudin (Iprivask™)

Interventions

Desirudin (Iprivask™) DRUG

Patients who are randomized to the desirudin (study) group will receive 15 mg of subcutaneous desirudin twice a day (at 0900 and 2100). These patients will also receive an injection of normal saline placebo at 1300 so that patients in both groups will receive three injections at the same time points.

Desirudin (Iprivask™)

Heparin DRUG

The patients who are randomized to the Heparin (standard of care) group will receive subcutaneous injections of heparin three times a day (0900, 1300 and 2100).

Heparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are scheduled for elective Cardiac or Thoracic Surgery.
• Age \> 18 years of age.

You may not qualify if:

• Patients with a clinical suspicion or a documented history of DVT/PE
• Patients who may require anticoagulation during the post-op period. (i.e. Patients with a history of A-fib, scheduled for a MAZE procedure or placement of a mechanical valve, or those on Coumadin/IV heparin preoperatively)
• Patients who have a history of HIT or if there is a suspicion of the patient having HIT pre-operatively.
• Documented allergy to heparin, desirudin, or lepirudin
• Patients with a history of coagulation disorder
• Platelet count\< 100 X109 /dl
• Active bleeding
• Serum Creatinine ≥ 1.5 mg/dl or CrCl ≤ 30 ml/min
• Patients with a baseline coagulopathy (INR \> 1.5 or aPTT \> 45 sec)
• Patients with liver disease
• Pregnancy
• Patients who require ventricular assist devices before or after surgery

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Barnes-Jewish Hospital: collaborator
• Canyon Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• Graetz TJ, Tellor BR, Smith JR, Avidan MS. Desirudin: a review of the pharmacology and clinical application for the prevention of deep vein thrombosis. Expert Rev Cardiovasc Ther. 2011 Sep;9(9):1101-9. doi: 10.1586/erc.11.131.

  PMID: 21932952 DERIVED

• Avidan MS, Smith JR, Skrupky LP, Hill L, Jacobsohn E, Burnside B, Tymkew H, Eby C, Damiano R, Despotis GJ. The occurrence of antibodies to heparin-platelet factor 4 in cardiac and thoracic surgical patients receiving desirudin or heparin for postoperative venous thrombosis prophylaxis. Thromb Res. 2011 Dec;128(6):524-9. doi: 10.1016/j.thromres.2011.05.025. Epub 2011 Jul 26.

  PMID: 21794899 DERIVED

MeSH Terms

Conditions

Venous Thrombosis

Interventions

desirudin; Heparin

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Limitations and Caveats

The study size was small and a surrogate end point was the primary outcome. The study was not powered to show statistical differences in clinical outcomes. Many patients received both desirudin and heparin during the study.

Results Point of Contact

• Title: Michael S. Avidan, MBBCh
• Organization: Washington University School of Medicine

avidanm@wustl.edu

314-747-4155

Study Officials

• Michael S Avidan, MBBCh

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Charles Hantler, MD

  Washington University School of Medicine

  STUDY DIRECTOR

• Bryan Meyers, MD

  Washington University School of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Study Record Dates

• First Submitted: May 22, 2006
• First Posted: May 24, 2006
• Study Start: May 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: March 5, 2019
• Results First Posted: June 13, 2011

Record last verified: 2011-06

Locations

US (1)