Antibiotic Loaded Calcium Sulfate RCT

NCT ID: NCT03875963

Last Updated: 2023-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-01

Study Completion Date

2022-11-23

Brief Summary

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This is a multi-centered, prospective, randomized controlled trial comparing current standard of care for defect management to placement of antibiotic loaded Stimulan as a bone void filler in patients undergoing treatment of infected tibial defects or infected tibial nonunions.

Detailed Description

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There is a tremendous burden of disease associated with infected bone defects and infected nonunions and their management is challenging. Infected bone defects and nonunions have a profound clinical and economic impact and outcomes are limited by high rates of re-operation and poor functional outcomes. Reconstruction of infected bone defects or nonunions is difficult with multiple treatment options that may be considered. A comprehensive approach includes the treatment of infection, the management of dead space, skeletal stabilization, stimulation of soft tissue healing and healing of the bone defect or nonunion.

There is little evidence and a distinct lack of consensus regarding the definitive management of infected bone defects and infected nonunions. A two stage approach is still the gold standard for management and it remains unclear when alternative approaches should be considered. The first stage of the procedure includes adequate debridement, skeletal stabilization as required and placement of a polymethyl methacrylate cement spacer with or without antibiotics at the site of the bone defect. The second stage typically occurs between 6-8 weeks later with removal of the cement spacer and bone grafting into the preserved defect. There is no clear preferred management strategy and there remains a significant evidence gap.

There has been a significant interest in the use of bone graft substitutes for defect management as part of the management of infected bone defects and infected nonunions. The use of calcium sulfate as an alternative synthetic bone graft material has long been established (1-4), and the combination of calcium sulfate with antibiotics has been reported in the literature almost as long as antibiotics have been available (5, 6).

The clinical performance of calcium sulfate in combination with a single antibiotic, Tobramycin, is well documented (7, 8). However, in recent years, the use of calcium sulfate in combination with multiple antibiotics has grown in use as a means of providing protection from bacterial colonization by a wider variety of gram negative and gram positive pathogens (9-12). This study will evaluate the clinical performance of a high purity calcium sulfate bone void filler, STIMULAN® Rapid Cure. STIMULAN® Rapid Cure is intended to be gently packed into bony voids or gaps of the skeletal system (i.e., extremities, pelvis, and posterolateral spine). STIMULAN® Rapid Cure provides a bone graft substitute that resorbs and is replaced with bone during the healing process. STIMULAN® Rapid Cure is biodegradable and biocompatible and may be used at an infected site.

The proposed study is a multi-centered, prospective, randomized controlled trial, comparing current standard of care for defect management to placement of antibiotic loaded Stimulan as a bone void filler in patients undergoing treatment of infected tibial defects or infected tibial nonunions. Patients with an infected tibial bone defect or infected tibial nonunion meeting inclusion criteria will be randomized to receive either standard of care for defect management (Group A) or placement of antibiotic loaded Stimulan (10cc Stimulan Rapid Cure, 1g Vancomycin, 240mg Tobramycin) as a bone void filler (Group B), with a standardized intervention and post-intervention protocol.

Conditions

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Fracture Non Union Infection

Keywords

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Infection Antibiotic bone cement Tibia nonunion

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The proposed study is a multi-centered, prospective, randomized controlled trial, comparing current standard of care for defect management to placement of antibiotic loaded Stimulan as a bone void filler in patients undergoing treatment of infected tibial defects or infected tibial nonunions.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Determination of union assessed by two independent assessors blinded to treatment arm

Study Groups

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Antibiotic loaded bone filler

Patients will undergo irrigation and debridement, surgical stabilization as required, and defect management by placement of antibiotic loaded Stimulan as a bone void filler \[calcium sulfate bone void filler (10 cc of STIMULAN(R) Rapid Cure, Biocomposites Ltd, UK) combined with the following antibiotic combination: 1g Vancomycin, 240mg Tobramycin\]. The concurrent use of antibiotics is at the discretion of the treating physician.

Group Type EXPERIMENTAL

Antibiotic loaded bone filler

Intervention Type OTHER

Defect management by placement of antibiotic loaded Stimulan as a bone void filler \[calcium sulfate bone void filler (10 cc of STIMULAN(R) Rapid Cure, Biocomposites Ltd, UK) combined with the following antibiotic combination: 1g Vancomycin, 240mg Tobramycin\].

Standard of care

Current standard of care treatment for infected tibial defects or infected tibial nonunions includes treatment with irrigation and debridement, surgical stabilization as required, and defect management as required including placement of a polymethyl methacrylate spacer with or without antibiotics. A second procedure may or may not occur 6-8 weeks later with removal of the cement spacer and bone grafting into the preserved defect. Concurrent use of antibiotics is at the discretion of the treating physician.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Antibiotic loaded bone filler

Defect management by placement of antibiotic loaded Stimulan as a bone void filler \[calcium sulfate bone void filler (10 cc of STIMULAN(R) Rapid Cure, Biocomposites Ltd, UK) combined with the following antibiotic combination: 1g Vancomycin, 240mg Tobramycin\].

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* ≥16 years old.
* Isolated infected tibia defect or infected tibial nonunion (characterized by clinical symptoms present for greater than 90 days, the presence of necrotic bone, and bacteria cultured from prior procedures, surgical biopsy, or draining sinuses).

Exclusion Criteria

* Presence of previous vascular injury or pathologic fracture
* Associated lower limb injuries that would interfere with rehabilitation or outcome
* Refusal to participate
* Inability to provide informed consent
* Inability to speak/understand or read English without a registered interpreter.
* Allergy or sensitivity to Vancomycin or Tobramycin
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biocomposites Ltd

INDUSTRY

Sponsor Role collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emil Schemitsch, MD FRCS(C)

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre

Locations

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London Health Sciences Centre

London, Ontario, Canada

Site Status

Countries

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Canada

References

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PELTIER LF. The use of plaster of paris to fill large defects in bone. Am J Surg. 1959 Mar;97(3):311-5. doi: 10.1016/0002-9610(59)90305-8. No abstract available.

Reference Type BACKGROUND
PMID: 13627355 (View on PubMed)

PELTIER LF. The use of plaster of Paris to fill defects in bone. Clin Orthop. 1961;21:1-31. No abstract available.

Reference Type BACKGROUND
PMID: 14485018 (View on PubMed)

PELTIER LF, BICKEL EY, LILLO R, THEIN MS. The use of plaster of paris to fill defects in bone. Ann Surg. 1957 Jul;146(1):61-9. doi: 10.1097/00000658-195707000-00007. No abstract available.

Reference Type BACKGROUND
PMID: 13435702 (View on PubMed)

Peltier LF, Jones RH. Treatment of unicameral bone cysts by curettage and packing with plaster-of-Paris pellets. J Bone Joint Surg Am. 1978 Sep;60(6):820-2.

Reference Type BACKGROUND
PMID: 701318 (View on PubMed)

KOVACEVIC B. [Problem of hematogenous osteomyelitis]. Langenbecks Arch Klin Chir Ver Dtsch Z Chir. 1953;276:432-43. No abstract available. Undetermined Language.

Reference Type BACKGROUND
PMID: 13143827 (View on PubMed)

Fischer G, Seidler W. [Results in the treatment of osteomyelitic bone cavities using antibiotic gypsum medullary plombage]. Dtsch Gesundheitsw. 1971 Nov 4;26(45):2105-7. No abstract available. German.

Reference Type BACKGROUND
PMID: 5145654 (View on PubMed)

McKee MD, Li-Bland EA, Wild LM, Schemitsch EH. A prospective, randomized clinical trial comparing an antibiotic-impregnated bioabsorbable bone substitute with standard antibiotic-impregnated cement beads in the treatment of chronic osteomyelitis and infected nonunion. J Orthop Trauma. 2010 Aug;24(8):483-90. doi: 10.1097/BOT.0b013e3181df91d9.

Reference Type BACKGROUND
PMID: 20657257 (View on PubMed)

McKee MD, Wild LM, Schemitsch EH, Waddell JP. The use of an antibiotic-impregnated, osteoconductive, bioabsorbable bone substitute in the treatment of infected long bone defects: early results of a prospective trial. J Orthop Trauma. 2002 Oct;16(9):622-7. doi: 10.1097/00005131-200210000-00002.

Reference Type BACKGROUND
PMID: 12368641 (View on PubMed)

Gauland C. Managing lower-extremity osteomyelitis locally with surgical debridement and synthetic calcium sulfate antibiotic tablets. Adv Skin Wound Care. 2011 Nov;24(11):515-23. doi: 10.1097/01.ASW.0000407647.12832.6c.

Reference Type BACKGROUND
PMID: 22015750 (View on PubMed)

Jogia RM, Modha DE, Nisal K, Berrington R, Kong MF. Use of highly purified synthetic calcium sulfate impregnated with antibiotics for the management of diabetic foot ulcers complicated by osteomyelitis. Diabetes Care. 2015 May;38(5):e79-80. doi: 10.2337/dc14-3100. No abstract available.

Reference Type BACKGROUND
PMID: 25908163 (View on PubMed)

Other Identifiers

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5148

Identifier Type: -

Identifier Source: org_study_id