Clinical trial NCT05294796: Efficacy and Safety of Antimicrobial Durations Treatment of Infections Associated With Osteosynthesis Material
Official title: Efficacy and Safety of Different Antimicrobial Durations for the Treatment of Infections Associated With Osteosynthesis Material Implanted After Long Bone Fractures (DURATIOM). Phase 3 Pragmatic Multicenter Open Labelled Randomized Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Infections
Keywords: Infections associated with osteosynthesis material
Fracture-related infection
Long bone fractures
Antibiotics duration
Antimicrobial therapy
Multidrug-resistant bacteria
Biofilm fracture healing
Antibiotic toxicity
Investigator-driven clinical trial
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2022-03-24
Enrollment: 364
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic, multicenter, non-inferiority, open labelled, randomized trial comparing different durations of antibiotherapy in osteosynthesis material infections after long bone fractures treated with debridement and material retention (see design algorithm and inclusion criteria). The CONSORT extension for pragmatic designs will be used.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with clinical cure in the test of cure
timeFrame: 12 months after completion of antimicrobial treatment
measure: Radiological healing in the test of cure
timeFrame: 12 months after completion of antimicrobial treatment
measure: Definitive soft tissue coverage at test of cure
timeFrame: 12 months after completion of antimicrobial treatment
Secondary outcomes:
measure: Efficacy of each group of antibiotics
timeFrame: 12 months from the start of antibiotic treatment
measure: Performance of an antibiogram to assess the development of antimicrobial resistance
timeFrame: 8 months and 12 months
measure: Surgical wound culture to assess the development of secondary infections
timeFrame: 8 months and 12 months
measure: Recurrence rate
timeFrame: 8 months and 12 months
measure: Evaluate the need for new surgeries, such as debridement, removal of material, coverage or amputation, through radiological evaluation of fracture union.
timeFrame: Day 28, week 8, week 12, month 6 and month 12.
measure: Evaluation of the functional status, defined as the recovery of the functionality of the limb prior to the fracture, by completing the Quick Disabilities of Arm, Shoulder and Hand questionnaire.
timeFrame: 6 months and 12 months (visit 6 and 7)
measure: Evaluation the consumption of health resources
timeFrame: Month 12
measure: Evaluate the number of patients who have required any of the bone or soft tissue reconstruction strategies.
timeFrame: Month 12
measure: Presentation of adverse events (frequency and severity).
timeFrame: Through study completion (12 months)
measure: Clostridium difficile infection
timeFrame: During treatment or 30 days after completion
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Sabadell
country: Spain
facility: Hospital Universitario Parc Taulí
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario Jerez de la Frontera
state: Cádiz
city: Palma
country: Spain
facility: Hospital Universitario Son Espases
state: Illes Balears
city: Logroño
country: Spain
facility: Hospital San Pedro
state: La Rioja
city: Ponferrada
country: Spain
facility: Hospital Universitario El Bierzo
state: León
city: Alcalá De Henares
country: Spain
facility: Hospital Universitario Príncipe de Asturias
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
state: Seville
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitario Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Cádiz
country: Spain
facility: Hospital Universitario Puerto Real
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Málaga
country: Spain
facility: Hospital Universitario Costa del Sol
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
Study officials:
affiliation: Hospital Universitario Virgen Macarena
name: María Dolores del Toro López
role: PRINCIPAL_INVESTIGATOR
References: