Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) (PARITY)

• ClinicalTrials.gov Identifier: NCT01479283
• Recruitment Status: Active, not recruiting
• First Posted: November 24, 2011
• Last Update Posted: November 8, 2019
• Sponsor: McMaster University
• 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, MD, FRCSC, McMaster University

Tracking Information

• First Submitted Date: November 15, 2011
• First Posted Date: November 24, 2011
• Last Update Posted Date: November 8, 2019
• Actual Study Start Date: January 2013
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 10, 2014)

Surgical Site Infections [ Time Frame: 1 year ]

the development of a surgical site infection according to the criteria established by the Center for Disease Control (CDC)

Original Primary Outcome Measures (submitted: November 23, 2011)

number of infections [ Time Frame: 1 year ]

the development of deep infection at the surgical site involving the prosthesis

Current Secondary Outcome Measures (submitted: October 10, 2014)

• Functional Outcome and Quality of Life [ Time Frame: 1 year ]
  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 ]
  examples of antibiotic-related complications include gastrointestinal infections, fungal infections, etc.
• Rate of Re-Operation [ Time Frame: 1 year ]
  re-operation may be required if patients develop a surgical site infection
• Oncologic Recurrence and/or Metastases [ Time Frame: 1 year ]
• Mortality [ Time Frame: 1 year ]

Original Secondary Outcome Measures (submitted: November 23, 2011)

• functional outcome and quality of life as measured by the MSTS-93 and TESS questionnaires [ Time Frame: 1 year ]
• number of antibiotic-related complications [ Time Frame: 1 year ]
  examples of antibiotic-related complications: gastrointestinal infections, fungal infections, etc.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY)
• 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
• Brief Summary: 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.
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Infection
• Bone Neoplasms

Intervention

• 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 ®
• 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 ®

Study Arms

• 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

  Intervention: Drug: 24-Hour Prophylactic Cefazolin* Antibiotic Regimen
• 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

  Intervention: Drug: 5-Days Prophylactic Cefazolin* Antibiotic Regimen

Publications *

• Hasan K, Racano A, Deheshi B, Farrokhyar F, Wunder J, Ferguson P, Holt G, Schwartz H, Petrisor B, Bhandari M, Ghert M. Prophylactic antibiotic regimens in tumor surgery (PARITY) survey. BMC Musculoskelet Disord. 2012 Jun 7;13:91. doi: 10.1186/1471-2474-13-91.
• Ghert M, Deheshi B, Holt G, Randall RL, Ferguson P, Wunder J, Turcotte R, Werier J, Clarkson P, Damron T, Benevenia J, Anderson M, Gebhardt M, Isler M, Mottard S, Healey J, Evaniew N, Racano A, Sprague S, Swinton M, Bryant D, Thabane L, Guyatt G, Bhandari M; PARITY Investigators. Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study. BMJ Open. 2012 Nov 28;2(6). pii: e002197. doi: 10.1136/bmjopen-2012-002197. Print 2012.
• Racano A, Pazionis T, Farrokhyar F, Deheshi B, Ghert M. High infection rate outcomes in long-bone tumor surgery with endoprosthetic reconstruction in adults: a systematic review. Clin Orthop Relat Res. 2013 Jun;471(6):2017-27. doi: 10.1007/s11999-013-2842-9. Epub 2013 Feb 12. Review.
• Evaniew N, Nuttall J, Farrokhyar F, Bhandari M, Ghert M. What are the levels of evidence on which we base decisions for surgical management of lower extremity bone tumors? Clin Orthop Relat Res. 2014 Jan;472(1):8-15. doi: 10.1007/s11999-013-3311-1. Epub 2013 Oct 1. Review.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 7, 2019): 602
• Original Estimated Enrollment (submitted: November 23, 2011): 100
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• primary bone malignancies or aggressive benign bone tumors of the femur or tibia, soft-tissue sarcomas which have invaded the femur or tibia, or oligometastatic bone disease of the femur or tibia in a patient expected to live at least one year post-operatively; and
• treatment by surgical excision and endoprosthetic replacement of the femur or tibia.

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);
• current surgical procedure is a revision surgery for implant failure or infection;
• 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 structural allograft;
• enrolled in a competing study; and
• weight of less than or equal to 45 kg (for sites using cefuroxime only).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Brazil, Canada, Egypt, India, Netherlands, Singapore, South Africa, Spain, United States
• Removed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01479283
• Other Study ID Numbers: GHRT01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Michelle Ghert, MD, FRCSC, McMaster University
• Study Sponsor: McMaster University

Collaborators

• 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

• PRS Account: McMaster University
• Verification Date: November 2019