Antibiotic Impregnated Bone Graft to Reduce Infection in Hip Replacement.

Study Overview
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Brief Summary
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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.

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

Conditions
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Arthroplasty, Replacement, Hip, Osteoarthritis, Hip, Antibiotic Resistant Infection, Prosthetic Joint Infection

Intervention / Treatment
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* Drug: Vancomycin + Tobramycin
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Hip arthroplasty requiring bone graft Willing to provide informed consent. For women of childbearing potential; a negative pregnancy test prior to reoperation. Exclusion Criteria: Ongoing prosthetic joint infection Known allergies and contraindications for the use of vancomycin or tobramycin Mental inability, reluctance, or language difficulties that according to investigator judgement, result in difficulty understanding the meaning of study participation Expected difficulties to complete 2-year follow-up Women of child bearing potential not using contraception Pregnant women Nursing women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A pragmatic, phase II, randomized, double-blind, placebo-controlled, multicenter drug trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>Combination of vancomycin and tobramycin mixed with allograft and locally administered during revision surgery after total hip arthroplasty. | Drug: Vancomycin + Tobramycin<br>* 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.<br>* Other names: Treatment;|
| Placebo Comparator: Placebo<br>Saline locally added to allograft and locally administered during revision surgery after total hip arthroplasty. | Drug: Saline<br>* As a placebo added to the allograft.<br>* Other names: Control;|

What is the study measuring?
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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. |