Antibiotic Impregnated Bone Graft to Reduce Infection in Hip Replacement. (ABOGRAFT)

Antibiotic Impregnated Bone Graft to Reduce Infection in Hip Replacement. The ABOGRAFT Trial

Total hip replacement is the most successful treatment modern healthcare can offer patients to regain quality of life. Periprosthetic joint infection (PJI) is the most common and devastating complication after total hip replacement (THR). Between 0.5 to 2% of primary THR (first time hip replacement), and 8-10% of revision THR (replacement of a hip prosthesis) will become infected.1 The introduction of local antibiotics blended into bone cement has led to a reduction in postoperative infection in primary THR by half.2 Unfortunately, cement can't always be used in relevant quantities.

The number of primary and revision surgeries of the hip is projected to increase dramatically. Therefore, the need for a feasible infection prophylaxis that is applicable for complex primary and revision THR in addition to antibiotics loaded cement is urgent.

Impacted morselized bone allograft is often used in (revision) THR to fill bone defects. Morselized allograft has been used as a carrier for local antibiotic treatment in multiple pilot studies and appears to be an attractive and effective treatment option, both for already infected joints and as a prophylactic measure in high-risk patients (e.g. THR revision surgeries). Nonetheless, a pivotal trial to support its use in THR is lacking. The aim of this pragmatic randomized controlled double blinded drug trial is to investigate whether antibiotic impregnated bone graft (AIBG) decreases the risk of infection after hip arthroplasty compared to controls treated with placebo impregnated bone graft. Patients scheduled for elective THR will be randomized to receive AIBG or a placebo impregnated bone graft. The primary outcome variable will be the number of re-operations due to infections and PJI diagnoses 2 years postoperative.

Study Overview

• Status: Recruiting
• Conditions: Prosthetic Joint Infection; Osteoarthritis, Hip; Antibiotic Resistant Infection; Arthroplasty, Replacement, Hip
• Intervention / Treatment: Drug: Saline; Drug: Vancomycin + Tobramycin

• Study Type: Interventional
• Enrollment (Estimated): 850
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Daphne Wezenberg, PhD; Phone Number: 0046101030000; Email: daphne.wezenberg@liu.se

Study Locations

• Sweden
  • Region Östergotland
    • Linköping, Region Östergotland, Sweden, 58185
      • Recruiting
      • Universitetssjukhuset Linköping
      • Contact: daphne Wezenberg, PhD; Phone Number: 0046 793345789; Email: daphne.wezenberg@liu.se
      • Contact: Jörg Schilcher, MD, PhD, Prof.; Phone Number: 0046 101034312; Email: jorg.schilcher@liu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Hip arthroplasty requiring bone graft
3. Willing to provide informed consent.
4. For women of childbearing potential; a negative pregnancy test prior to reoperation.

Exclusion Criteria:

1. Ongoing prosthetic joint infection
2. Known allergies and contraindications for the use of vancomycin or tobramycin
3. Mental inability, reluctance, or language difficulties that according to investigator judgement, result in difficulty understanding the meaning of study participation
4. Expected difficulties to complete 2-year follow-up
5. Women of child bearing potential not using contraception
6. Pregnant women
7. Nursing women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm; Combination of vancomycin and tobramycin mixed with allograft and locally administered during revision surgery after total hip arthroplasty.	Drug: Vancomycin + Tobramycin; 1 g vancomycin (powder) diluted in 8 ml tobramycin (80mg/ml). Added to the prepared allograft before the allograft is used during the revision surgery.; Other Names: Treatment
Placebo Comparator: Placebo; Saline locally added to allograft and locally administered during revision surgery after total hip arthroplasty.	Drug: Saline; As a placebo added to the allograft.; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reoperation due to infection or diagnosed PJI with bacteria that are sensitive to either vancomycin or tobramycin, in the same hip joint, within two years after hip arthroplasty.	Reoperation due to infection or diagnosed PJI 2 years of revision surgery.	2 years after finalizing data collection.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time and cause for reoperation for any reason within 2 and 5 years	Time and cause for reoperation for any reason within 2 and 5 years	2 and 5 years after finalizing data collection.
Time and cause for implant revision due to any reason within 2 and 5 years	Time and cause for implant revision due to any reason within 2 and 5 years	2 and 5 years after finalizing data collection.
Type of microbe and antibiotic resistance pattern for cases complicated with postoperative infection	Type of microbe and antibiotic resistance pattern for cases complicated with postoperative infection	2 and 5 years after finalizing data collection.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences between the two experimental groups regarding the frequencies of adverse events	Differences between the two experimental groups regarding the frequencies of adverse events	2 and 5 years after finalizing data collection.
Differences between the two experimental groups regarding the rates of revision due to aseptic loosening	Differences between the two experimental groups regarding the rates of revision due to aseptic loosening	2 and 5 years after finalizing data collection.

Collaborators and Investigators

• Sponsor: University Hospital, Linkoeping
• Collaborators: The Swedish Research Council; Region Östergötland
• Investigators: Principal Investigator: Jörg Schilcher, PhD, Linkoeping University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: December 9, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 23, 2021

Study Record Updates

• Last Update Posted (Estimated): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Infections; Communicable Diseases; Osteoarthritis, Hip; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Tobramycin
• Other Study ID Numbers: ABOGRAFT-01; 2021-001708-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No