Clinical trial NCT06402292: Surgical Treatment of Osteoarticular Infections Using Bioactive Bone Substitute
Official title: Outcomes of Surgical Treatment of Osteoarticular Infections Using Bioactive Bone Substitute Impregnated With Antibiotics: Prospective Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Osteomyelitis
Infections
Fracture
Antibiotics
Keywords: infection
osteomyelitis
fracture
local antibiotics
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
First posted: 2024-05-07
Enrollment: 25
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This prospective research project aims to evaluate the effectiveness and clinical outcomes of utilizing antibiotic-impregnated bioactive bone substitute (PerOssal®) in the surgical management of osteoarticular infections. Osteoarticular infections pose significant challenges in orthopaedic surgery due to the risk of persistent infection, bone loss, and functional impairment. Traditional treatment approaches involve extensive debridement followed by systemic antibiotic therapy and bone grafting. However, antibiotic-impregnated bioactive bone substitutes offer a promising alternative by providing local antibiotic delivery and promoting bone regeneration simultaneously. This study will prospectively enrol patients undergoing surgical intervention for osteoarticular infections and assess their clinical outcomes, including infection resolution, bone healing, functional recovery, and complication rates. Comprehensive data collection will include preoperative patient characteristics, intraoperative details, postoperative outcomes, and long-term follow-up assessments. Statistical analyses will be performed to compare outcomes between patients treated with antibiotic-impregnated bioactive bone substitute and those past managed with traditional methods. The findings of this study are expected to contribute valuable insights into the effectivennes and safety of this novel approach, potentially informing future clinical practices and optimizing patient care in the management of osteoarticular infections.

Detailed description: Background:

Osteoarticular infections represent a significant challenge in orthopedic surgery, posing substantial morbidity and potential mortality if not adequately managed. These infections can arise from various sources, including hematogenous spread, contiguous spread from adjacent soft tissue or bone, or direct inoculation during trauma or surgery. Common pathogens associated with osteoarticular infections include Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus species, and gram-negative bacilli, among others.

The management of osteoarticular infections typically involves a combination of surgical intervention and antimicrobial therapy. Surgical treatment aims to achieve complete debridement of infected tissue, removal of necrotic bone, and restoration of skeletal integrity. However, achieving adequate debridement and local antibiotic delivery while preserving bone stock remains a challenge.

Traditional approaches to bone defect management often rely on autografts, allografts, or synthetic bone substitutes. While these methods have demonstrated efficacy in promoting bone healing, they may not address the specific challenges posed by osteoarticular infections, particularly in terms of infection eradication and local antibiotic delivery.

In recent years, there has been growing interest in the use of antibiotic-impregnated bioactive bone substitutes for the management of osteoarticular infections. These materials offer several potential advantages over traditional approaches. Firstly, they provide a scaffold for bone regeneration, promoting osteogenesis and osteoconduction. Secondly, they have the capacity to release antibiotics locally, achieving high concentrations at the site of infection while minimizing systemic exposure and potential adverse effects. Thirdly, they can fill osseous defects and provide structural support, facilitating functional recovery.

The efficacy of antibiotic-impregnated bioactive bone substitutes in the treatment of osteoarticular infections has been investigated in several preclinical and clinical studies. Preclinical studies have demonstrated the ability of these materials to effectively deliver antibiotics, inhibit bacterial growth, and promote bone healing in animal models of osteomyelitis and septic arthritis. Clinical studies have reported promising results, including high rates of infection resolution, bone healing, and functional recovery, with low rates of recurrence and complications.

However, despite these promising findings, there remains a need for further research to evaluate the long-term outcomes and comparative effectiveness of antibiotic-impregnated bioactive bone substitutes in the surgical management of osteoarticular infections. Additionally, questions regarding the optimal selection of antibiotics, the timing and duration of local antibiotic delivery, and the potential for antibiotic resistance warrant investigation.

Therefore, this prospective research project aims to address these gaps in knowledge by evaluating the outcomes of surgical treatment of osteoarticular infections using antibiotic-impregnated bioactive bone substitutes in a well-defined patient population. By systematically assessing clinical outcomes, including infection resolution, bone healing, functional recovery, and complication rates, this study seeks to provide evidence-based insights into the efficacy and safety of this novel approach. Ultimately, the findings of this study may have implications for clinical practice, guiding the optimization of surgical management strategies for osteoarticular infections and improving patient outcomes.

Hypothesis The utilization of antibiotic-impregnated bioactive bone substitute reduces recurrence in patients with osteoarticular infections compared to untreated patients. It presents clinical non-inferiority and decreases hospitalization time in relation to the use of PMMA, as it does not require another surgical procedure for material removal.

Clinical Question:

PICOS Strategy P (Patients): Patients above 12 years old with fracture-related infection (FRI) and indication for surgical treatment.

I (Intervention): Orthopedic surgical treatment with standard local debridement, supplemented with implantation of antibiotic-impregnated bioactive bone substitute (PerOssal®).

C (Control): Retrospective cohort of previously operated patients without the use of local treatment or with the use of antibiotic-loaded PMMA.

O (Outcomes):

Primary: Comparative rate of infection recurrence within 1-year follow-up. Secondary: Pain score, quality of life, overall complications, microbiological profile of infections, duration of systemic antibiotic usage, length of hospital stay.

S (Study): Prospective cohort.

Methods:

This is an observational, prospective, single-center study. The methodology will be guided by the STROBE checklist and the study submitted to the Plataforma Brasil and Ethics Committee. Data will be collected using RedCap® Protocol.

Sample size calculation: For comparison of relative risk between groups, expecting a mean difference of 20% in infection recurrence rate between patients without local antibiotic treatment and patients with local treatment, the expected necessary number of patients is 20. Accounting for a 20% loss to follow-up, the required number of patients in the study will be 25.

Statistical Analysis:

Quantitative Variables:

* T-test and ANOVA for parametric data.
* Mann-Whitney or Kruskal-Wallis tests for non-parametric data.

Qualitative Variables:

- Fischer's exact test.

Relative Risk:

- Cox regression.

Descriptive Values:

- Mean and standard deviation; 95% confidence interval.

Statistical Significance:

- p \< 0.05.

Eligibility criteria: Inclusion Criteria:

All fracture-related infections (clinical and laboratory/microbiological diagnosis).

Patients \> 12 years old.

Surgical treatment with indication for local antibiotic use.

Exclusion Criteria:

Other modalities of musculoskeletal infection (arthroplasties, hematogenous osteomyelitis, septic arthritis, infections related to bone tumors).

Unconfirmed diagnosis of infection.

Primary outcomes:
measure: Comparative rate of infection recurrence
timeFrame: 1 YEAR
Secondary outcomes:
measure: Pain score using numeric pain scale (0 - no pain; 10 - worst pain)
timeFrame: 6,12, 24, 48 WEEKS
measure: QUALITY OF LIFE USING EuroQol-5D (EQ-5D)
timeFrame: 6,12, 24, 48 WEEKS
measure: General complications (other than infection recurrence)
timeFrame: 6,12, 24, 48 WEEKS
measure: Microbiological profile of infections
timeFrame: up to 1 week
measure: Duration of systemic antibiotic usage
timeFrame: up to 12 weeks
measure: Length of hospital stay
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
Study officials:
affiliation: PROFESSOR
name: GUILHERME FALOTICO, PhD
role: PRINCIPAL_INVESTIGATOR
References: