Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY)

Infection Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01479283
• Other study ID #: GHRT01
• Status: Completed
• Phase: Phase 3
• Start date: January 2013
• Est. completion date: March 2021

Study information

• Verified date: March 2021
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 602
• Est. completion date: March 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Bone Neoplasms
• Infection

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.
• 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.

Locations

Country	Name	City	State
Argentina	Hospital Universitario Austral	Pilar	Buenos Aires
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Austria	LKH - Universitätsklinikum Graz	Graz
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	Instituto de Ortopedia e Traumatologia	São Paulo
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Juravinski Hospital and Cancer Centre	Hamilton	Ontario
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Hôtel-Dieu de Québec	Québec City	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Egypt	Children's Cancer Hospital Egypt	Cairo
India	All India Institute of Medical Sciences	New Delhi	Delhi
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden	South Holland
Singapore	Singapore General Hospital	Singapore
South Africa	Grey's Hospital	Pietermaritzburg
Spain	Hospital Universitari Vall d'Hebron	Barcelona
United States	Albany Medical Center	Albany	New York
United States	Emory Orthopaedics and Spine Center	Atlanta	Georgia
United States	Franklin Square Medical Center	Baltimore	Maryland
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	The Cleveland Clinic - Hillcrest Hospital	Cleveland	Ohio
United States	Wexner Medical Center	Columbus	Ohio
United States	SUNY Upstate University Hospital	East Syracuse	New York
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	University of Florida Health Shands Hospital	Gainesville	Florida
United States	Hartford Hospital	Hartford	Connecticut
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	Medical College of Wisconsin - Froedtert Hospital	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	The Rothman Institute at Jefferson	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University Hospital	Portland	Oregon
United States	Long Island Jewish Medical Center | Northwell Health	Queens	New York
United States	Stanford University Hospital and Clinics	Redwood City	California
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of California San Francisco Medical Center	San Francisco	California

Sponsors (5)

Lead Sponsor	Collaborator
McMaster University	Canadian Cancer Society (CCS), Canadian Institutes of Health Research (CIHR), Orthopedic Research and Education Foundation, The Physicians' Services Incorporated Foundation

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Egypt,  India,  Netherlands,  Singapore,  South Africa,  Spain, 

References & Publications (4)

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. — View 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). pii: e002197. doi: 10.1136/bmjopen-2012-002197. Print 2012. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Antibiotic-Related Complications	examples of antibiotic-related complications include gastrointestinal infections, fungal infections, etc.	1 year
Secondary	Rate of Re-Operation	re-operation may be required if patients develop a surgical site infection	1 year
Secondary	Oncologic Recurrence and/or Metastases		1 year
Secondary	Mortality		1 year