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

Overview

Journal Trials

Publisher Biomed Central

Specialties General Medicine
Pharmacology

Date 2021 Mar 23

PMID 33752752

Citations 4

Authors

Patricia Schneider

Diane Heels-Ansdell

Lehana Thabane

Michelle Ghert

Affiliations

Soon will be listed here.

Abstract

Background: Limb salvage with endoprosthetic reconstruction is the current standard practice for the surgical management of lower extremity bone tumors in skeletally mature patients and typically includes tumor resection followed by the functional limb reconstruction with modular metallic and polyethylene endoprosthetic implants. However, owing to the complexity and length of these procedures, as well as the immunocompromised nature of patients treated with chemotherapy, the risk of surgical site infection (SSI) is high. The primary research objective of the Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial is to assess whether a 5-day regimen of post-operative antibiotics decreases the risk of SSI at 1 year post-operatively compared to a 1-day regimen. This article describes the statistical analysis plan for the PARITY trial.

Methods/design: The PARITY trial is an ongoing multi-center, blinded parallel two-arm randomized controlled trial (RCT) of 600 participants who have been diagnosed with a primary bone tumor, a soft tissue sarcoma that has invaded the bone or oligometastatic bone disease of the femur or tibia that requires surgical resection and endoprosthetic reconstruction. This article describes the overall analysis principles, including how participants will be included in each analysis, the presentation of results, adjustments for covariates, the primary and secondary outcomes, and their respective analyses. Additionally, we will present the planned sensitivity and sub-group analyses.

Discussion: Our prior work has demonstrated (1) high rates of SSI after the treatment of lower extremity tumors by surgical excision and endoprosthetic reconstruction, (2) highly varied opinion and practice among orthopedic oncologists with respect to prophylactic antibiotic regimens, (3) an absence of applicable RCT evidence, (4) extensive support from international investigators to participate in a RCT, and (5) the feasibility of conducting a definitive RCT to evaluate a 5-day regimen of post-operative antibiotics in comparison with a 1-day regimen.

Trial Registration: ClinicalTrials.gov NCT01479283 . Registered on 24 November 2011.

Citing Articles

CORR Insights®: Can Periprosthetic Joint Infection of Tumor Prostheses Be Controlled With Debridement, Antibiotics, and Implant Retention?.

Allison D Clin Orthop Relat Res. 2024; 483(1):59-61.

PMID: 39240086 PMC: 11658719. DOI: 10.1097/CORR.0000000000003236.

High Risk for Persistent Peri-Prosthetic Infection and Amputation in Mega-Prosthesis Reconstruction.

Berger C, Parai C, Tillander J, Bergh P, Wennergren D, Brisby H J Clin Med. 2023; 12(10).

PMID: 37240683 PMC: 10218797. DOI: 10.3390/jcm12103575.

Postoperative Complication and Reoperation Rates Following Resection of Soft Tissue vs. Bone Malignancies Based on Anatomic Location in the Inpatient Setting.

Ballatori A, Shahrestani S, Ton A, Chen X, Yamout T, Gettleman B Sarcoma. 2023; 2023:5455719.

PMID: 36937506 PMC: 10023224. DOI: 10.1155/2023/5455719.

Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial.

Ghert M, Schneider P, Guyatt G, Thabane L, Velez R, OShea T JAMA Oncol. 2022; 8(3):345-353.

PMID: 34989778 PMC: 8739829. DOI: 10.1001/jamaoncol.2021.6628.

References

Montori V, Devereaux P, Adhikari N, Burns K, Eggert C, Briel M . Randomized trials stopped early for benefit: a systematic review. JAMA. 2005; 294(17):2203-9. DOI: 10.1001/jama.294.17.2203. View

Jeys L, Grimer R, Carter S, Tillman R . Risk of amputation following limb salvage surgery with endoprosthetic replacement, in a consecutive series of 1261 patients. Int Orthop. 2003; 27(3):160-3. PMC: 3458454. DOI: 10.1007/s00264-003-0429-x. View

Jakobsen J, Gluud C, Wetterslev J, Winkel P . When and how should multiple imputation be used for handling missing data in randomised clinical trials - a practical guide with flowcharts. BMC Med Res Methodol. 2017; 17(1):162. PMC: 5717805. DOI: 10.1186/s12874-017-0442-1. View

Gutowski C, Zmistowski B, Clyde C, Parvizi J . The economics of using prophylactic antibiotic-loaded bone cement in total knee replacement. Bone Joint J. 2014; 96-B(1):65-9. DOI: 10.1302/0301-620X.96B1.31428. View

. Prophylactic antibiotic regimens in tumour surgery (PARITY): a pilot multicentre randomised controlled trial. Bone Joint Res. 2015; 4(9):154-62. PMC: 4602191. DOI: 10.1302/2046-3758.49.2000482. View

Ruggieri P, Mavrogenis A, Mercuri M . Quality of life following limb-salvage surgery for bone sarcomas. Expert Rev Pharmacoecon Outcomes Res. 2011; 11(1):59-73. DOI: 10.1586/erp.10.91. View

Sun X, Briel M, Walter S, Guyatt G . Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. BMJ. 2010; 340:c117. DOI: 10.1136/bmj.c117. View

Gamble C, Krishan A, Stocken D, Lewis S, Juszczak E, Dore C . Guidelines for the Content of Statistical Analysis Plans in Clinical Trials. JAMA. 2017; 318(23):2337-2343. DOI: 10.1001/jama.2017.18556. View

Akahane T, Shimizu T, Isobe K, Yoshimura Y, Fujioka F, Kato H . Evaluation of postoperative general quality of life for patients with osteosarcoma around the knee joint. J Pediatr Orthop B. 2007; 16(4):269-72. DOI: 10.1097/BPB.0b013e3280925670. View

10.

Tunn P, Pomraenke D, Goerling U, Hohenberger P . Functional outcome after endoprosthetic limb-salvage therapy of primary bone tumours--a comparative analysis using the MSTS score, the TESS and the RNL index. Int Orthop. 2007; 32(5):619-25. PMC: 2551713. DOI: 10.1007/s00264-007-0388-8. View

11.

Schreiber D, Bell R, Wunder J, OSullivan B, Turcotte R, Masri B . Evaluating function and health related quality of life in patients treated for extremity soft tissue sarcoma. Qual Life Res. 2006; 15(9):1439-46. DOI: 10.1007/s11136-006-0001-4. View

12.

Reddy K, Wafa H, Gaston C, Grimer R, Abudu A, Jeys L . Does amputation offer any survival benefit over limb salvage in osteosarcoma patients with poor chemonecrosis and close margins?. Bone Joint J. 2015; 97-B(1):115-20. DOI: 10.1302/0301-620X.97B1.33924. View

13.

Moher D, Hopewell S, Schulz K, Montori V, Gotzsche P, Devereaux P . CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010; 340:c869. PMC: 2844943. DOI: 10.1136/bmj.c869. View

14.

Jarvinen T, Sihvonen R, Bhandari M, Sprague S, Malmivaara A, Paavola M . Blinded interpretation of study results can feasibly and effectively diminish interpretation bias. J Clin Epidemiol. 2014; 67(7):769-72. DOI: 10.1016/j.jclinepi.2013.11.011. View

15.

Thabane L, Mbuagbaw L, Zhang S, Samaan Z, Marcucci M, Ye C . A tutorial on sensitivity analyses in clinical trials: the what, why, when and how. BMC Med Res Methodol. 2013; 13:92. PMC: 3720188. DOI: 10.1186/1471-2288-13-92. View

16.

Wang R, Lagakos S, Ware J, Hunter D, Drazen J . Statistics in medicine--reporting of subgroup analyses in clinical trials. N Engl J Med. 2007; 357(21):2189-94. DOI: 10.1056/NEJMsr077003. View

17.

Briel M, Lane M, Montori V, Bassler D, Glasziou P, Malaga G . Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2). Trials. 2009; 10:49. PMC: 2723099. DOI: 10.1186/1745-6215-10-49. View

18.

Ghert M, Deheshi B, Holt G, Randall R, Ferguson P, Wunder J . Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study. BMJ Open. 2012; 2(6). PMC: 3533099. DOI: 10.1136/bmjopen-2012-002197. View

19.

Hasan K, Racano A, Deheshi B, Farrokhyar F, Wunder J, Ferguson P . Prophylactic antibiotic regimens in tumor surgery (PARITY) survey. BMC Musculoskelet Disord. 2012; 13:91. PMC: 3461415. DOI: 10.1186/1471-2474-13-91. View

20.

Davis A, Wright J, Williams J, Bombardier C, Griffin A, Bell R . Development of a measure of physical function for patients with bone and soft tissue sarcoma. Qual Life Res. 1996; 5(5):508-16. DOI: 10.1007/BF00540024. View