Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY)

NCT ID: NCT01479283

Last Updated: 2021-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 602 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2021-03-31

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.

Conditions

Infection; Bone Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

24-Hour Prophylactic Cefazolin* Antibiotic Regimen

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

5-Days Prophylactic Cefazolin* Antibiotic Regimen

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

ANCEF ®; ANCEF ®

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).

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orthopedic Research and Education Foundation

OTHER

Sponsor Role: collaborator

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role: collaborator

Canadian Cancer Society (CCS)

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Michelle Ghert, MD, FRCSC

Professor | Department of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michelle Ghert, MD, FRCSC

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Saint Louis University Hospital

St Louis, Missouri, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Stanford University Hospital and Clinics

Redwood City, California, United States

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

University of California San Francisco Medical Center

San Francisco, California, United States

University of Connecticut Health Center

Farmington, Connecticut, United States

Hartford Hospital

Hartford, Connecticut, United States

University of Florida Health Shands Hospital

Gainesville, Florida, United States

Emory Orthopaedics and Spine Center

Atlanta, Georgia, United States

Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Franklin Square Medical Center

Baltimore, Maryland, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Albany Medical Center

Albany, New York, United States

SUNY Upstate University Hospital

East Syracuse, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Long Island Jewish Medical Center | Northwell Health

Queens, New York, United States

Montefiore Medical Center

The 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

Oregon Health & Science University Hospital

Portland, Oregon, United States

The Rothman Institute at Jefferson

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Vanderbilt Medical Center

Nashville, Tennessee, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Medical College of Wisconsin - Froedtert Hospital

Milwaukee, Wisconsin, United States

Hospital Universitario Austral

Pilar, Buenos Aires, Argentina

Royal Adelaide Hospital

Adelaide, South Australia, Australia

LKH - Universitätsklinikum Graz

Graz, , Austria

Hospital de Clínicas de Porto Alegre

Porto Alegre, , Brazil

Instituto de Ortopedia e Traumatologia

São Paulo, , Brazil

Foothills Medical Centre

Calgary, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Juravinski Hospital and Cancer Centre

Hamilton, Ontario, Canada

Ottawa Hospital

Ottawa, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Hôtel-Dieu de Québec

Québec, Quebec, Canada

Children's Cancer Hospital Egypt

Cairo, , Egypt

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, India

Leiden University Medical Center

Leiden, South Holland, Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Singapore General Hospital

Singapore, , Singapore

Grey's Hospital

Pietermaritzburg, , South Africa

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Countries

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

References

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.

Reference Type: BACKGROUND

PMID: 22676321 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23194956 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23404421 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24081669 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34989778 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33752752 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33743753 (View on PubMed)

Other Identifiers

GHRT01

Identifier Type: -

Identifier Source: org_study_id