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

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

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.

Study Overview

• Status: Completed
• Conditions: Bone Neoplasms; Infection
• Intervention / Treatment: Drug: 24-Hour Prophylactic Cefazolin* Antibiotic Regimen; Drug: 5-Days Prophylactic Cefazolin* Antibiotic Regimen

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
• Enrollment (Actual): 602
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, 1629
      • Hospital Universitario Austral
• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
• Austria
  • Graz, Austria
    • LKH - Universitätsklinikum Graz
• Brazil
  • Porto Alegre, Brazil
    • Hospital de Clínicas de Porto Alegre
  • São Paulo, Brazil
    • Instituto de Ortopedia e Traumatologia
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5A1
      • Foothills Medical Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Vancouver General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Hospital and Cancer Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University Health Centre
    • Montreal, Quebec, Canada, H1T4B3
      • Maisonneuve-Rosemont Hospital
    • Québec City, Quebec, Canada, G1R 2J6
      • Hotel-Dieu de Quebec
• Egypt
  • Cairo, Egypt
    • Children's Cancer Hospital Egypt
• India
  • Delhi
    • New Delhi, Delhi, India
      • All India Institute of Medical Sciences
• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen
  • South Holland
    • Leiden, South Holland, Netherlands, 2333
      • Leiden University Medical Center
• Singapore
  • Singapore, Singapore
    • Singapore General Hospital
• South Africa
  • Pietermaritzburg, South Africa
    • Grey's Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90404
      • Ronald Reagan UCLA Medical Center
    • Redwood City, California, United States, 94063
      • Stanford University Hospital and Clinics
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • San Francisco, California, United States, 94118
      • University of California San Francisco Medical Center
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center
    • Hartford, Connecticut, United States, 06106
      • Hartford Hospital
  • Florida
    • Gainesville, Florida, United States, 32611-2727
      • University of Florida Health Shands Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory Orthopaedics and Spine Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Holden Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Albany, New York, United States, 11206
      • Albany Medical Center
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • East Syracuse, New York, United States, 13057
      • SUNY Upstate University Hospital
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • Queens, New York, United States, 11040
      • Long Island Jewish Medical Center | Northwell Health
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic - Hillcrest Hospital
    • Columbus, Ohio, United States, 43210
      • Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • The Rothman Institute at Jefferson
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232-8774
      • Vanderbilt Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin - Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: ANCEF ®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Site Infections	the development of a surgical site infection according to the criteria established by the Center for Disease Control (CDC)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		1 year
Functional Outcome and Quality of Life	as measured by the Musculoskeletal Tumor Society (MSTS) functional score (1987 and 1993 versions) and the Toronto Extremity Salvage Score (TESS) questionnaires	1 year
Antibiotic-Related Complications	examples of antibiotic-related complications include gastrointestinal infections, fungal infections, etc.	1 year
Rate of Re-Operation	re-operation may be required if patients develop a surgical site infection	1 year
Oncologic Recurrence and/or Metastases		1 year

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR); Canadian Cancer Society (CCS); The Physicians' Services Incorporated Foundation; Orthopedic Research and Education Foundation

Publications and helpful links

General 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):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.
• 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.
• Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) Investigators; Ghert M, Schneider P, Guyatt G, Thabane L, Velez R, O'Shea T, Randall RL, Turcotte R, Wilson D, Wunder JS, Baptista AM, Cheng EY, Doung YC, Ferguson PC, Giglio V, Hayden J, Heels-Ansdell D, Khan SA, Sampath Kumar V, McKay P, Miller B, van de Sande M, Zumarraga JP, Bhandari M. Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial. JAMA Oncol. 2022 Mar 1;8(3):345-353. doi: 10.1001/jamaoncol.2021.6628.
• Schneider P, Heels-Ansdell D, Thabane L, Ghert M; PARITY Investigators. Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY): a multi-center randomized controlled study comparing alternative antibiotic regimens in patients undergoing tumor resections with endoprosthetic replacements-a statistical analysis plan. Trials. 2021 Mar 22;22(1):223. doi: 10.1186/s13063-021-05147-2.
• Gazendam A, Bozzo A, Schneider P, Giglio V, Wilson D, Ghert M. Recruitment patterns in a large international randomized controlled trial of perioperative care in cancer patients. Trials. 2021 Mar 20;22(1):219. doi: 10.1186/s13063-021-05149-0.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: November 23, 2011
• First Posted (Estimate): November 24, 2011

Study Record Updates

• Last Update Posted (Actual): March 11, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Infection; Randomized; Prosthesis; Anti-Bacterial Agents; Bone Neoplasms
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Musculoskeletal Diseases; Bone Diseases; Bone Neoplasms; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular; Cefazolin
• Other Study ID Numbers: GHRT01

Plan for Individual participant data (IPD)

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