Daptomycin Use for Antimicrobial Prophylaxis in Methicillin Resistant Staphylococcus Aureus (MRSA) Colonized Adult Patients Undergoing Primary Elective Hip, Knee, or Shoulder Arthroplasty

NCT01196169 | Terminated Phase 4 DMC

• 1 other identifier: 0310.7f
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This study will evaluate the safety and effectiveness of daptomycin, an antibiotic compared to another one which is vancomycin when given around the time of joint replacement surgery. Vancomycin is recommended for perioperative prophylaxis in methicillin resistant Staphylococcus aureus (MRSA) colonized patients undergoing primary total joint arthroplasty. Daptomycin has not been recommended for this indication but it is FDA approved for treatment of MRSA blood stream and skin and soft tissue infections. Data collected during this study may support the use of daptomycin for this indication and may also be used for other research purposes that have not yet been specified.

Conditions

Staphylococcal Infections; Methicillin-resistant Staphylococcus Aureus

Keywords

daptomycin; vancomycin; perioperative; prophylaxis; arthroplasty; prosthesis; preoperative

Outcome Measures

Primary Outcomes (1)

• Daptomycin efficacy in prevention of postoperative surgical site infection (SSI)

  Efficacy of daptomycin in preventing postoperative SSI will be determined for each enrolled subject on one month postoperative visit. Overall efficacy of daptomycin among the patient group who receive it will be compared to overall efficacy of vancomycin among the second patient group who receive vancomycin upon anticipated complete enrollment study at 24 months.

  24 months

Secondary Outcomes (1)

• Efficacy of daptomycin in preventing postoperative early prosthetic joint infection

  30 months

Study Arms (2)

Daptomycin

EXPERIMENTAL

Half of patients anticipated to be enrolled will receive daptomycin in antimicrobial prophylaxis prior to their prosthetic joint surgery.

Drug: Daptomycin

Vancomycin

ACTIVE COMPARATOR

Half of patients anticipated to be enrolled will receive vancomycin in antimicrobial prophylaxis prior to their prosthetic joint surgery.

Drug: Vancomycin

Interventions

Daptomycin DRUG

One dose of Daptomycin 6 mg/Kg iv, will be infused over 30 minutes. The infusion will start no longer than one hour prior to surgical incision of primary knee or hip prosthetic joint arthroplasty.

Also known as: Cubicin

Daptomycin

Vancomycin DRUG

Two doses of vancomycin 15 mg/Kg iv, with a maximum of 2 grams with each dose be infused over 60-120 minutes according to the dose. The first dose infusion will start no longer than one hour (if ≤ one gram), or no longer than two hours (if \> one gram) prior to surgical incision of primary knee or hip prosthetic joint arthroplasty. A second similar dose will be given 12 hours after the first dose unless the patient has a creatinine clearance of \< 50 ml/min. Patients with creatinine clearance of \< 50 ml/min will only receive one dose.

Vancomycin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, and dated informed consent as defined by the Institutional Review Board.
• Male and female patients older than 18 years of age undergoing primary elective hip, knee or shoulder arthroplasty.
• Documented nasal carriage of MRSA.
• If a female of childbearing potential the patient should agree to practice a reliable contraceptive method (e.g. birth control pills, condoms, or intrauterine device \[IUD\]) during treatment and for one month after receiving the study medication.

You may not qualify if:

• Concurrent urinary tract infection or colonization unless treated with evidence of microbiologic cure.
• Evidence of active infection elsewhere other than urinary tract, unless treated with evidence of microbiologic cure documented by the infectious diseases service.
• Patients undergoing elective secondary arthroplasty.
• Concurrent open wounds
• Pregnant and nursing women (if patient is still of childbearing potential, a negative serum pregnancy test will be confirmed).
• History of allergy or contraindication to study drugs.
• Weight \>150 kg or \<50kg
• Patients with creatinine clearance (CLcr) \< 30ml/min (calculated using the Cockcroft-Gault equation using ideal body weight)
• Severe neutropenia (absolute neutrophil count \<0.500x103 /µl).
• Patients considered unlikely to comply with study procedures or to return for the scheduled post treatment evaluation.
• Ongoing antibiotic therapy for active infection that is anticipated to continue until the day of surgery.
• Any other condition that in the opinion of the investigator, would confound or interfere with evaluation of safety or efficacy of the investigational medication, or prevent compliance with the study protocol.

Sponsors & Collaborators

• Mountain Home Research & Education Corporation: lead
• East Tennessee State University: collaborator
• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): collaborator

Study Sites (2)

Johnson City Medical Center

Johnson City, Tennessee, 37604, United States

Location

James H Quillen VA Medical Center

Mountain Home, Tennessee, 37684, United States

Location

Related Publications (5)

• Bratzler DW, Houck PM; Surgical Infection Prevention Guidelines Writers Workgroup; American Academy of Orthopaedic Surgeons; American Association of Critical Care Nurses; American Association of Nurse Anesthetists; American College of Surgeons; American College of Osteopathic Surgeons; American Geriatrics Society; American Society of Anesthesiologists; American Society of Colon and Rectal Surgeons; American Society of Health-System Pharmacists; American Society of PeriAnesthesia Nurses; Ascension Health; Association of periOperative Registered Nurses; Association for Professionals in Infection Control and Epidemiology; Infectious Diseases Society of America; Medical Letter; Premier; Society for Healthcare Epidemiology of America; Society of Thoracic Surgeons; Surgical Infection Society. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis. 2004 Jun 15;38(12):1706-15. doi: 10.1086/421095. Epub 2004 May 26.

  PMID: 15227616 BACKGROUND

• Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004 Oct 14;351(16):1645-54. doi: 10.1056/NEJMra040181. No abstract available.

  PMID: 15483283 BACKGROUND

• Price CS, Williams A, Philips G, Dayton M, Smith W, Morgan S. Staphylococcus aureus nasal colonization in preoperative orthopaedic outpatients. Clin Orthop Relat Res. 2008 Nov;466(11):2842-7. doi: 10.1007/s11999-008-0337-x. Epub 2008 Jun 19.

  PMID: 18563506 BACKGROUND

• Lamp KC, Friedrich LV, Mendez-Vigo L, Russo R. Clinical experience with daptomycin for the treatment of patients with osteomyelitis. Am J Med. 2007 Oct;120(10 Suppl 1):S13-20. doi: 10.1016/j.amjmed.2007.07.010.

  PMID: 17904946 BACKGROUND

• Marculescu CE, Osmon DR. Antibiotic prophylaxis in orthopedic prosthetic surgery. Infect Dis Clin North Am. 2005 Dec;19(4):931-46. doi: 10.1016/j.idc.2005.07.002.

  PMID: 16297740 BACKGROUND

MeSH Terms

Conditions

Staphylococcal Infections

Interventions

Daptomycin; Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Glycopeptides; Glycoconjugates; Carbohydrates

Study Officials

• Wael E Shams, M.D.

  James H Quillen VA Medical Center and East Tennessee State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2010
• First Posted: September 8, 2010
• Study Start: October 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: February 3, 2014

Record last verified: 2014-01

Locations

US (2)