Clinical trial NCT01479283: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infection
Bone Neoplasms
Keywords: Infection
Bone Neoplasms
Prosthesis
Anti-Bacterial Agents
Randomized
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Orthopedic Research and Education Foundation
name: The Physicians' Services Incorporated Foundation
name: Canadian Cancer Society (CCS)
name: Canadian Institutes of Health Research (CIHR)
First posted: 2011-11-24
Enrollment: 602
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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).

Primary outcomes:
measure: Surgical Site Infections
timeFrame: 1 year
Secondary outcomes:
measure: Functional Outcome and Quality of Life
timeFrame: 1 year
measure: Antibiotic-Related Complications
timeFrame: 1 year
measure: Rate of Re-Operation
timeFrame: 1 year
measure: Oncologic Recurrence and/or Metastases
timeFrame: 1 year
measure: Mortality
timeFrame: 1 year
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Redwood City
country: United States
facility: Stanford University Hospital and Clinics
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Health Shands Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory Orthopaedics and Spine Center
state: Georgia
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Franklin Square Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Hospital
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: East Syracuse
country: United States
facility: SUNY Upstate University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Queens
country: United States
facility: Long Island Jewish Medical Center | Northwell Health
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic - Hillcrest Hospital
state: Ohio
city: Columbus
country: United States
facility: Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University Hospital
state: Oregon
city: Philadelphia
country: United States
facility: The Rothman Institute at Jefferson
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Froedtert Hospital
state: Wisconsin
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
state: Buenos Aires
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Graz
country: Austria
facility: LKH - Universitätsklinikum Graz
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: São Paulo
country: Brazil
facility: Instituto de Ortopedia e Traumatologia
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Hospital and Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Québec City
country: Canada
facility: Hôtel-Dieu de Québec
state: Quebec
city: Cairo
country: Egypt
facility: Children's Cancer Hospital Egypt
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: South Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Pietermaritzburg
country: South Africa
facility: Grey's Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
affiliation: McMaster University
name: Michelle Ghert, MD, FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.