Efficacy and Safety of Antimicrobial Durations Treatment of Infections Associated With Osteosynthesis Material (DURATIOM)

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Status and phase: Enrolling; Phase 3

Conditions: Infections

Treatments: Combination Product: Short course of antibiotherapy; Combination Product: Long course of antibiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05294796

DURATIOM

Details and patient eligibility

About

Infections associated with osteosynthesis material are among the most feared and challenging complications of trauma surgery and can lead to total function loss or limb amputation when complete recovery is to be expected without infection.

This is a clinical trial with the purpose of evaluate the optimal duration of antibiotic therapy in Infections Associated With Osteosynthesis Material Implanted when implant is retained.

Full description

Orthopedic implants for fracture fixation or osteosynthesis material are used for internal fixation of fractures, allowing their stability and consolidation.

Infection associated with osteosynthesis material is one of the most feared and challenging complications of trauma surgery and can lead to total loss of function or amputation of the limb, when complete recovery is to be expected without infection. Furthermore, they involve excessive consumption of antimicrobials, with inadequate prescriptions and prolonged durations that favour superinfections by multidrug-resistant microorganisms, in addition to the drug-related toxicities, especially diarrhea due to Clostridium difficile. Most studies and recommendations on the management of orthopedic implant-associated infections have focused on prosthetic joint infections, and while they share similarities with Infections Associated With Osteosynthesis Material Implanted, there are major differences in terms of risk factors, diagnosis, treatment, and prevention. While the extrapolation of knowledge from prosthetic joint infections to the field of Infections Associated With Osteosynthesis Material Implanted has helped orthopedic surgeons and internists/infectologists in their management, there are large gaps and unanswered questions that represent a new challenge for research in this field. One of these challenges, and focusing on the field of infection treatment, is the search for the best surgical procedure according to the age of the implant and fracture healing, to determine the duration of antibiotic treatment and whether it should be maintained until fracture healing, and which is the most appropriate treatment in each of the scenarios.

The identification of conditions in which the duration of the antimicrobial treatment can be shortened, and in case of prolonged treatments, which antimicrobial has the best safety profile and less impact on the induction of bacterial resistances is of special interest, due to the frequent appearance of toxicities and the increase of bacterial resistances and superinfections by multidrug-resistant bacteria.

If the hypothesis of non-inferiority of short vs. long antibiotic treatments is demonstrated, and the efficacy of antibiotics with less ecological impact in long treatments, the impact on reduction of bacterial resistance, toxicity and health costs will be observed. The project also aims to promote quality and multidisciplinary care, homogenising clinical practice in the management of Infections Associated With Osteosynthesis Material Implanted based on scientific knowledge. Early and personalised patient care with Infections Associated With Osteosynthesis Material Implanted allows for faster recovery, both clinically and functionally, enabling earlier mobility recovery.

Enrollment: 364 estimated patients

Sex: All

Ages: 14+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age greater than or equal to 14 years.
• Stable fracture, even if unconsolidated.
• Controlled infection (absence of signs or symptoms of sepsis).
• Early or delayed infection.
• Availability of antibiotics active against the isolated microorganism.
• Absence of bone exposure. Patients who initially had bone exposure but during the debridement surgery bone coverage was performed by any method (skin approximation, grafting, vacuum therapy) can be included in the criteria.
• Signed written informed consent.
• If there is a possibility of pregnancy (in women of childbearing potential) or paternity, agree to use a highly effective method of birth control recommended by the Clinical Trial Facilitation Group (CTFG) during the treatment phase of the trial

Exclusion criteria

• Late infections
• Infections of osteosynthesis material in non-long bones.
• Infections of revision osteosynthesis material or occurring after previous surgeries.
• Patients who are not expected to be followed up for at least 1 year after completion of antibiotic treatment.
• Pregnant or lactating women.
• Patients in whom there may be drug interactions or contraindications described in the technical data sheets of the investigational drugs used in this trial.
• Infections due to mycobacteria, fungi and parasites (since they are infections that are treated with drugs and for different durations).
• Patients in whom all the material is replaced during the debridement at the same surgical time (since these patients require antibiotic treatment for less than 8 weeks in all cases).
• Infections of external fixators.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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364 participants in 2 patient groups

Short course of antibiotherapy

Active Comparator group

Description:

Patients enrolled in this arm, will receive 8 weeks of antibiotherapy in case of early infection (\< 2 week), and 12 weeks of antibiotherapy in case of delayed infection (2-10 weeks)

Treatment:

Combination Product: Short course of antibiotherapy

Long course of antibiotherapy

Active Comparator group

Description:

Patients enrolled in this arm, will receive 12 weeks of antibiotherapy in case of early infection (\< 2 week), and until fracture healing of antibiotherapy in case of delayed infection

Treatment:

Combination Product: Long course of antibiotherapy