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Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by McMaster University
Sponsor:
Collaborators:
Orthopedic Research and Education Foundation
The Physicians' Services Incorporated Foundation
Canadian Cancer Society Research Institute (CCSRI)
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Michelle Ghert, McMaster University
ClinicalTrials.gov Identifier:
NCT01479283
First received: November 15, 2011
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

The Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial is the first ever international multi-center randomized controlled trial in bone cancer surgery. In order to avoid amputation for bone cancer in the leg, complex limb-saving operations are performed. However, infections with devastating complications following surgery are common. Surgeons from across the world will randomize patients to receive either short- or long-duration antibiotic regimens after surgery with the goal of identifying the best regimen to reduce these infections.


Condition Intervention Phase
Infection
Bone Neoplasms
Drug: 24-Hour Prophylactic Cefazolin* Antibiotic Regimen
Drug: 5-Days Prophylactic Cefazolin* Antibiotic Regimen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY): A Multi-Center International Randomized Controlled Trial Comparing Alternative Antibiotic Regimens in Patients Undergoing Tumor Resections With Endoprosthetic Replacements

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Surgical Site Infections [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    the development of a surgical site infection according to the criteria established by the Center for Disease Control (CDC)


Secondary Outcome Measures:
  • Functional Outcome and Quality of Life [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    as measured by the Musculoskeletal Tumor Society (MSTS) functional score (1987 and 1993 versions) and the Toronto Extremity Salvage Score (TESS) questionnaires

  • Antibiotic-Related Complications [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    examples of antibiotic-related complications include gastrointestinal infections, fungal infections, etc.

  • Rate of Re-Operation [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    re-operation may be required if patients develop a surgical site infection

  • Oncologic Recurrence and/or Metastases [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: January 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Short-Arm Antibiotic Regimen

Intervention: 24-Hour Prophylactic Cefazolin* Antibiotic Regimen

*or another cephalosporin with equivalent gram-positive coverage in centers where cefazolin is not routinely used or not approved for use

Drug: 24-Hour Prophylactic Cefazolin* Antibiotic Regimen

Pre-Operative Antibiotic Regimen: Patients will receive 2g (or a weight-based dose based on 100mg/kg/day with a maximum single dose of 2g if < 18 years old) of IV cefazolin within 60 minutes prior to the procedure. No other pre-operative antibiotics will be administered.

Intra-Operative Antibiotic Regimen: Patients will receive 2g (or a weight-based dose based on 100mg/kg/day with a maximum single dose of 2g if < 18 years old) of IV cefazolin every 3-4 hours. No other intra-operative antibiotics will be administered.

Post-Operative Antibiotic Regimen: Patients will receive 2g (or a weight-based dose based on 100mg/kg/day with a maximum single dose of 2g if < 18 years old) of IV cefazolin every 8 hours for 24 hours followed by IV saline for 4 days. No other post-operative antibiotics will be administered.

Other Name: ANCEF ®
Experimental: Long-Arm Antibiotic Regimen

Intervention: 5-Days Prophylactic Cefazolin* Antibiotic Regimen

*or another cephalosporin with equivalent gram-positive coverage in centers where cefazolin is not routinely used or not approved for use

Drug: 5-Days Prophylactic Cefazolin* Antibiotic Regimen

Pre-Operative Antibiotic Regimen: Patients will receive 2g (or a weight-based dose based on 100mg/kg/day with a maximum single dose of 2g if < 18 years old) of IV cefazolin within 60 minutes prior to the procedure. No other pre-operative antibiotics will be administered.

Intra-Operative Antibiotic Regimen: Patients will receive 2g (or a weight-based dose based on 100mg/kg/day with a maximum single dose of 2g if < 18 years old) of IV cefazolin every 3-4 hours. No other intra-operative antibiotics will be administered.

Post-Operative Antibiotic Regimen: Patients will receive 2g (or a weight-based dose based on 100mg/kg/day with a maximum single dose of 2g if < 18 years old) of IV cefazolin every 8 hours for 5 days. No other post-operative antibiotics will be administered.

Other Name: ANCEF ®

Detailed Description:

Long-bone sarcomas were historically managed with amputation. In the current era of osteosarcoma management, amputations are generally avoided by complex surgeries in which the malignancy is removed and the limb is reconstructed with advanced surgical techniques. This process of limb salvage is possible with improvements in chemotherapeutic regimens, advanced imaging techniques and surgical innovations such as modular metallic implants. However, the risk for surgical complications is high due to the complexity of the surgeries themselves. The most common and devastating complication is a surgical site infection. Background work and data from our pilot study indicates that infection rates approach 15%. Multiple surgical attempts at eradication of the infection fail in 50% of these cases, resulting in amputation. Published guidelines for post-operative antibiotic prophylaxis following many standard and less complex elective surgical procedures dictate that prophylactic antibiotics be discontinued after 24 hours. However, the most effective duration of treatment in sarcoma surgery has not previously been examined. Given the limitations of the evidence, it has not been possible for orthopaedic oncologists to draw firm conclusions and, therefore, clinical practice is highly varied, particularly with respect to antibiotic duration. Our international, multi-center randomized controlled trial will determine whether a 5-day regimen of post-operative prophylactic antibiotics in comparison to a standard 24-hour regimen decreases the rate of surgical site infections after limb salvage surgery within 1-year follow-up.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • primary malignant or aggressive benign bone tumors of the lower extremity, or soft-tissue sarcomas which have invaded the bone; and
  • treatment by surgical excision and endoprosthetic replacement.

Exclusion Criteria:

  • current known Methicillin-resistant Staphylococcus Aureus (MRSA) colonization;
  • current known Vancomycin Resistant Enterococcus (VRE) colonization;
  • documented anaphylaxis or angioedema to penicillin or cefazolin (Ancef);
  • prior surgery within the surgical field of the affected limb (excluding biopsy);
  • prior local infection within the surgical field of the affected limb;
  • current known immunologically-deficient disease conditions (not including recent chemotherapy);
  • known renal insufficiency with estimated creatinine clearance (eGRF) of less than 54 mL/min;
  • reconstruction to include allograft;
  • enrolled in a competing study; and
  • weight of less than or equal to 45 kg.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01479283

Contacts
Contact: Paula McKay, B.Sc (905) 527-4322 ext 44131 mckayp@mcmaster.ca
Contact: Tricia Schneider, B.Sc (905) 527-4322 ext 44983 schnep@mcmaster.ca

  Show 30 Study Locations
Sponsors and Collaborators
McMaster University
Orthopedic Research and Education Foundation
The Physicians' Services Incorporated Foundation
Canadian Cancer Society Research Institute (CCSRI)
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Michelle Ghert, MD, FRCSC McMaster University
  More Information

Publications:
Responsible Party: Michelle Ghert, Associate Professor, McMaster University
ClinicalTrials.gov Identifier: NCT01479283     History of Changes
Other Study ID Numbers: GHRT01
Study First Received: November 15, 2011
Last Updated: October 10, 2014
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by McMaster University:
Infection
Bone Neoplasms
Prosthesis
Anti-Bacterial Agents
Randomized

Additional relevant MeSH terms:
Bone Neoplasms
Infection
Neoplasms
Bone Diseases
Musculoskeletal Diseases
Neoplasms by Site
Anti-Bacterial Agents
Antibiotics, Antitubercular
Cefazolin
Anti-Infective Agents
Antitubercular Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014