Direct Thrombin Inhibitors Versus LMWH in Staphylococcus Aureus Bacteraemia

Direct Thrombin Inhibitors Versus LMWH in Staphylococcus Aureus Bacteraemia. A Prospective Randomized Controlled Academic Single-centre Feasibility Study.

Safety and efficacy of direct thrombin inhibitors versus enoxaparin in patients with staphylococcus aureus bacteraemia.

The study hypothesizes that inhibition of the coagulase-activity of S. aureus by direct thrombin inhibitors is safe and translates into a better outcome of patients with S. aureus bacteremia.

Study Overview

• Status: Completed
• Conditions: Staphylococcus Aureus Bacteraemia
• Intervention / Treatment: Drug: enoxaparin; Drug: direct thrombin inhibition

Detailed Description

Single center randomized controlled trial of direct thrombin inhibitors versus standard enoxaparin.

• Feasibility: proportion of patients eligible for randomization; clinically attained concentration of DTI and resulting staphylothrombin inhibition
• Safety: bleeding events (major/ clinically relevant non-major)
• Efficacy: thrombotic events during the thromboprophylactic treatment + 3 days

• Secondary outcome measures

  • Coagulation parameters: evolution of D-dimers from day 0-4; other lab parameters of coagulation (PT/APTT/fibrinogen/platelet count)
  • Inflammatory parameters: CRP, white blood cell count, neutrophilia
  • Clinical outcomes: metastatic infections, assessed clinically or by PET/CT; relapse of S. aureus bacteremia; defervescence; persistent positive blood cultures; hospital stay, mortality.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • KUleuven/UZ Gasthuisberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Positive blood culture for staphylococcus aureus
• Symptoms or signs of infection
• Indication for thromboprophylaxis

Exclusion Criteria:

• Contraindication for thromboprophylaxis
• Significant active bleeding or risk of excessive bleeding
• Heparin-induced thrombocytopenia
• Severe liver and kidney disease
• Pregnancy and lactation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: direct thrombin inhibition; dabigatran 110 mg BID, po argatroban (0.5 - 1 µg/kg/min) if peroral therapy is not possible	Drug: direct thrombin inhibition; Other Names: dabigatran; argatroban
Active Comparator: enoxaparin; enoxaparin 40 mg od, sc	Drug: enoxaparin; Other Names: clexane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary Safety Outcome is the occurence of clinically-relevant bleeding events	From date of randomization up to end of study drug + 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary efficacy outcome is the occurence of metastatic infection	as documented with a PET-CTscan in eligible patients on D7-10 or clinically-overt metastatic infectious foci	From randomization until month 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laboratory markers of coagulation	D-dimeren, fibrinogen, APTT, PT dabigatran level or antiXa	From randomization until D7-10
Laboratory markers of inflammation	CRP	From randomization until D7-10
Clinical outcomes after S. aureus bacteremia		From randomization until M3

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Peter Verhamme, Doctor, Bloedings-en vaatziekten, UZ Gasthuisberg

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: June 14, 2013
• First Submitted That Met QC Criteria: July 25, 2013
• First Posted (Estimate): July 30, 2013

Study Record Updates

• Last Update Posted (Estimate): July 13, 2016
• Last Update Submitted That Met QC Criteria: July 11, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Sepsis; Bacteremia; Staphylococcal Infections; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Hemostatics; Coagulants; Thrombin; Dabigatran; Enoxaparin; Argatroban
• Other Study ID Numbers: S54881

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED