A Pilot Study of Daptomycin for Antimicrobial Prophylaxis

A Pilot Study of Daptomycin for Antimicrobial Prophylaxis in Patients Undergoing Cardiac Valve Replacement and Coronary Artery Bypass Grafting (CABG) Who Are at Increased Risk for Infection Due to Methicillin-resistant Staphylococcus Aureus (MRSA)

The goals of the study are to evaluate the feasibility of using daptomycin as a prophylactic antimicrobial agent in patients undergoing cardiac surgery, to determine the rates of surgical site infection, and to evaluate the occurrence of adverse events.

Study Overview

• Status: Terminated
• Conditions: Antimicrobial Prophylaxis
• Intervention / Treatment: Drug: daptomycin 6 mg/kg IV

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

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: Patients will be eligible for inclusion in the study if they meet the following criteria:

1. Provide signed and dated informed consent and are willing to receive the study medication
2. Age ≥ 18 years of age

3. If a female of childbearing potential is willing to practice at least one method of birth control during treatment and for at least 28 days after treatment with study medication:

   1. barrier methods of birth control (e.g., condoms, diaphragms together with spermicidal foam or gel, or presence of IUD) or

   2. surgical sterilization, approved hormonal contraceptives (such as birth control pills, depo-Provera, or Lupron Depot), or IUD are all acceptable.

      • Rhythm, temperature, and verbal promise of abstinence are not acceptable methods of birth control.
4. If a female of childbearing potential, serum HCG negative within 24 hours of scheduled surgery.

5. Planned cardiac surgery procedures meeting current Duke criteria to receive anti-microbial prophylaxis active against MRSA:

   a. Patients will meet at least one of the following criteria which are the same as for prophylaxis with vancomycin: i. preoperative hospitalization > 48 hours ii. transfer to Duke from outside facility iii. previous history of MRSA iv. any patient deemed to be high risk for MRSA by the attending surgeon, due to a complicated past medical and/or surgical history

EXCLUSION CRITERIA: Patients who satisfy any of the following are not eligible for study enrollment.

1. Hypersensitivity to daptomycin
2. Inability to receive standard prophylaxis agents (cefuroxime and rifampin) for any reason
3. Staphylococcal bacteremia at the time of enrollment
4. Diagnosis of S. aureus or coagulase negative staphylococcus pacemaker/defibrillator infection within the preceding 18 months
5. Patient is undergoing emergency CABG
6. Weight >150 kg or <50kg
7. Patients considered unlikely to survive at least 7 days due to underlying illness.
8. Patients with creatinine clearance (CLcr) < 30mL/min (calculated using the Cockcroft-Gault equation using actual body weight)
9. Severe neutropenia (absolute neutrophil count <0.500x103 /µL)
10. Pregnant, nursing or lactating women (if patient is still of childbearing potential, a negative serum pregnancy test will be confirmed)
11. Patients considered unlikely to comply with study procedures or to return for the scheduled post treatment evaluation
12. Any other condition that in the opinion of an investigator, would confound or interfere with evaluation of safety or efficacy of the investigational medication, or prevent compliance with the study protocol

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Daptomycin as a single preoperative dose within 30 minutes prior to surgery Dosage: if creatinine clearance ≥ 30 ml/min: 6 mg/kg IV	Drug: daptomycin 6 mg/kg IV; daptomycin 6 mg/kg IV given during induction phase as a one-time prophylactic dose for patients undergoing cardiac valve replacement and coronary artery bypass grafting (CABG) who are at increased risk for infection due to methicillin-resistant Staphylococcus aureus (MRSA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of Patients Receiving Antimicrobial Prophylaxis Within the Appropriate Timeframe Before Incision	30 days after surgery

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Cubist Pharmaceuticals LLC
• Investigators: Principal Investigator: Keith S Kaye, MD, MPH, DMC

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: December 12, 2007
• First Submitted That Met QC Criteria: December 12, 2007
• First Posted (Estimate): December 13, 2007

Study Record Updates

• Last Update Posted (Estimate): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: MRSA; Increased risk for infection
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: Pro00000856; 19497 (Other Identifier: City of Hope Medical Center)