Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) (PARITY)
Primary Purpose
Infection, Bone Neoplasms
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
24-Hour Prophylactic Cefazolin* Antibiotic Regimen
5-Days Prophylactic Cefazolin* Antibiotic Regimen
Sponsored by
About this trial
This is an interventional prevention trial for Infection focused on measuring Infection, Bone Neoplasms, Prosthesis, Anti-Bacterial Agents, Randomized
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).
Sites / Locations
- University of Arkansas for Medical Sciences
- Ronald Reagan UCLA Medical Center
- Stanford University Hospital and Clinics
- UC Davis Comprehensive Cancer Center
- University of California San Francisco Medical Center
- University of Connecticut Health Center
- Hartford Hospital
- University of Florida Health Shands Hospital
- Emory Orthopaedics and Spine Center
- Holden Comprehensive Cancer Center
- University of Maryland Medical Center
- Sinai Hospital of Baltimore
- Franklin Square Medical Center
- Johns Hopkins Hospital
- Massachusetts General Hospital
- Boston Children's Hospital
- Beth Israel Deaconess Medical Center
- University of Minnesota Medical Center
- Saint Louis University Hospital
- Dartmouth-Hitchcock Medical Center
- Albany Medical Center
- Montefiore Medical Center
- SUNY Upstate University Hospital
- Memorial Sloan-Kettering Cancer Center
- Long Island Jewish Medical Center | Northwell Health
- Cincinnati Children's Hospital
- The Cleveland Clinic - Hillcrest Hospital
- Wexner Medical Center
- Oregon Health & Science University Hospital
- The Rothman Institute at Jefferson
- University of Pittsburgh Medical Center
- Vanderbilt Medical Center
- Huntsman Cancer Institute
- Medical College of Wisconsin - Froedtert Hospital
- Hospital Universitario Austral
- Royal Adelaide Hospital
- LKH - Universitätsklinikum Graz
- Hospital de Clínicas de Porto Alegre
- Instituto de Ortopedia e Traumatologia
- Foothills Medical Centre
- Vancouver General Hospital
- Juravinski Hospital and Cancer Centre
- Ottawa Hospital
- Mount Sinai Hospital
- Maisonneuve-Rosemont Hospital
- McGill University Health Centre
- Hôtel-Dieu de Québec
- Children's Cancer Hospital Egypt
- All India Institute of Medical Sciences
- Leiden University Medical Center
- University Medical Center Groningen
- Singapore General Hospital
- Grey's Hospital
- Hospital Universitari Vall d'Hebron
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Short-Arm Antibiotic Regimen
Long-Arm Antibiotic Regimen
Arm Description
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: 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
Outcomes
Primary Outcome Measures
Surgical Site Infections
the development of a surgical site infection according to the criteria established by the Center for Disease Control (CDC)
Secondary Outcome Measures
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
Antibiotic-Related Complications
examples of antibiotic-related complications include gastrointestinal infections, fungal infections, etc.
Rate of Re-Operation
re-operation may be required if patients develop a surgical site infection
Oncologic Recurrence and/or Metastases
Mortality
Full Information
NCT ID
NCT01479283
First Posted
November 15, 2011
Last Updated
March 9, 2021
Sponsor
McMaster University
Collaborators
Orthopedic Research and Education Foundation, The Physicians' Services Incorporated Foundation, Canadian Cancer Society (CCS), Canadian Institutes of Health Research (CIHR)
1. Study Identification
Unique Protocol Identification Number
NCT01479283
Brief Title
Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY)
Acronym
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
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
January 2013 (Actual)
Primary Completion Date
March 2021 (Actual)
Study Completion Date
March 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McMaster University
Collaborators
Orthopedic Research and Education Foundation, The Physicians' Services Incorporated Foundation, Canadian Cancer Society (CCS), Canadian Institutes of Health Research (CIHR)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infection, Bone Neoplasms
Keywords
Infection, Bone Neoplasms, Prosthesis, Anti-Bacterial Agents, Randomized
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
602 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Short-Arm Antibiotic Regimen
Arm Type
Active Comparator
Arm Description
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
Arm Title
Long-Arm Antibiotic Regimen
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
24-Hour Prophylactic Cefazolin* Antibiotic Regimen
Other Intervention Name(s)
ANCEF ®
Intervention Description
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
Intervention Name(s)
5-Days Prophylactic Cefazolin* Antibiotic Regimen
Other Intervention Name(s)
ANCEF ®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Surgical Site Infections
Description
the development of a surgical site infection according to the criteria established by the Center for Disease Control (CDC)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Functional Outcome and Quality of Life
Description
as measured by the Musculoskeletal Tumor Society (MSTS) functional score (1987 and 1993 versions) and the Toronto Extremity Salvage Score (TESS) questionnaires
Time Frame
1 year
Title
Antibiotic-Related Complications
Description
examples of antibiotic-related complications include gastrointestinal infections, fungal infections, etc.
Time Frame
1 year
Title
Rate of Re-Operation
Description
re-operation may be required if patients develop a surgical site infection
Time Frame
1 year
Title
Oncologic Recurrence and/or Metastases
Time Frame
1 year
Title
Mortality
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michelle Ghert, MD, FRCSC
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Stanford University Hospital and Clinics
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
UC Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California San Francisco Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94118
Country
United States
Facility Name
University of Connecticut Health Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
Facility Name
Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
University of Florida Health Shands Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611-2727
Country
United States
Facility Name
Emory Orthopaedics and Spine Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Franklin Square Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21237
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Minnesota Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
Facility Name
Saint Louis University Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Albany Medical Center
City
Albany
State/Province
New York
ZIP/Postal Code
11206
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
SUNY Upstate University Hospital
City
East Syracuse
State/Province
New York
ZIP/Postal Code
13057
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Long Island Jewish Medical Center | Northwell Health
City
Queens
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
The Cleveland Clinic - Hillcrest Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oregon Health & Science University Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
The Rothman Institute at Jefferson
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-8774
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Medical College of Wisconsin - Froedtert Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Hospital Universitario Austral
City
Pilar
State/Province
Buenos Aires
ZIP/Postal Code
1629
Country
Argentina
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
LKH - Universitätsklinikum Graz
City
Graz
Country
Austria
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
Country
Brazil
Facility Name
Instituto de Ortopedia e Traumatologia
City
São Paulo
Country
Brazil
Facility Name
Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 5A1
Country
Canada
Facility Name
Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Juravinski Hospital and Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Mount Sinai Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
Facility Name
Maisonneuve-Rosemont Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T4B3
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1A4
Country
Canada
Facility Name
Hôtel-Dieu de Québec
City
Québec City
State/Province
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Facility Name
Children's Cancer Hospital Egypt
City
Cairo
Country
Egypt
Facility Name
All India Institute of Medical Sciences
City
New Delhi
State/Province
Delhi
Country
India
Facility Name
Leiden University Medical Center
City
Leiden
State/Province
South Holland
ZIP/Postal Code
2333
Country
Netherlands
Facility Name
University Medical Center Groningen
City
Groningen
Country
Netherlands
Facility Name
Singapore General Hospital
City
Singapore
Country
Singapore
Facility Name
Grey's Hospital
City
Pietermaritzburg
Country
South Africa
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
22676321
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.
Results Reference
background
PubMed Identifier
23194956
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.
Results Reference
background
PubMed Identifier
23404421
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.
Results Reference
background
PubMed Identifier
24081669
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.
Results Reference
background
PubMed Identifier
34989778
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.
Results Reference
derived
PubMed Identifier
33752752
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.
Results Reference
derived
PubMed Identifier
33743753
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.
Results Reference
derived
Learn more about this trial
Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY)
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