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

August 27, 2024 updated by: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

364

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Barcelona, Spain, 08003
        • Recruiting
        • Hospital del Mar
        • Contact:
        • Principal Investigator:
          • Luisa Sorlí Redó
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitario Vall d'Hebron
        • Contact:
        • Principal Investigator:
          • María Dolores Rodríguez Pardo
      • Barcelona, Spain, 08041
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau
        • Contact:
        • Principal Investigator:
          • Natividad de Benito Hernández
      • Barcelona, Spain, 08907
        • Recruiting
        • Hospital Universitari de Bellvitge
        • Contact:
        • Principal Investigator:
          • Oscar Murillo Rubio
      • Barcelona, Spain, 08036
        • Recruiting
        • Hospital Universitario Clínic de Barcelona
        • Contact:
        • Principal Investigator:
          • Laura Morata ruiz
      • Cádiz, Spain, 11510
        • Recruiting
        • Hospital Universitario Puerto Real
        • Contact:
        • Principal Investigator:
          • Alberto Romero Palacios
      • Granada, Spain, 18014
        • Recruiting
        • Hospital Universitario Virgen de las Nieves
        • Contact:
        • Principal Investigator:
          • Concepción Fernández Roldán
      • Lugo, Spain, 27003
        • Recruiting
        • Hospital Universitario Lucus Augusti
        • Contact:
        • Principal Investigator:
          • María José García País
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon y Cajal
        • Contact:
        • Principal Investigator:
          • Javier Cobo Reinoso
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
        • Principal Investigator:
          • Jaime Lora-Tamayo Morillo-Velarde
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundacion Jimenez Diaz
        • Contact:
        • Principal Investigator:
          • Antonio Blanco García
      • Madrid, Spain, 28046
        • Terminated
        • Hospital Universitario La Paz
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Universitario Virgen de la Victoria
        • Contact:
        • Principal Investigator:
          • Enrique Nuño Álvarez
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Regional Universitario de Málaga
        • Contact:
        • Principal Investigator:
          • Beatriz Sobrino Díaz
      • Málaga, Spain, 29603
        • Recruiting
        • Hospital Universitario Costa del Sol
        • Contact:
        • Principal Investigator:
          • Alfonso del Arco Jiménez
      • Sevilla, Spain, 41014
        • Recruiting
        • Hospital Universitario Virgen de Valme
        • Contact:
        • Principal Investigator:
          • Juan E Corzo Delgado
      • Seville, Spain, 41009
      • Zaragoza, Spain, 50009
        • Recruiting
        • Hospital Clínico Universitario Lozano Blesa
        • Contact:
        • Principal Investigator:
          • José Ramón Paño Pardo
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Recruiting
        • Hospital Universitario Germans Trias i Pujol
        • Contact:
        • Principal Investigator:
          • Esteban Alberto Reynaga Sosa
      • Sabadell, Barcelona, Spain, 08208
        • Recruiting
        • Hospital Universitario Parc Taulí
        • Contact:
        • Principal Investigator:
          • Eva Van den Eynde Otero
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Recruiting
        • Hospital Universitario Marques de Valdecilla
        • Contact:
        • Principal Investigator:
          • Marta Fernández Sampedro
    • Cádiz
      • Jerez De La Frontera, Cádiz, Spain, 11407
        • Recruiting
        • Hospital Universitario Jerez de la Frontera
        • Contact:
        • Principal Investigator:
          • Virginia Corbacho Sánchez
    • Illes Balears
      • Palma, Illes Balears, Spain, 07120
        • Recruiting
        • Hospital Universitario Son Espases
        • Contact:
        • Principal Investigator:
          • Helem Haydeen Vilchez Rueda
    • La Rioja
      • Logroño, La Rioja, Spain, 26006
        • Recruiting
        • Hospital San Pedro
        • Contact:
        • Principal Investigator:
          • José Ramón Blanco Ramos
    • León
      • Ponferrada, León, Spain, 24404
        • Recruiting
        • Hospital Universitario El Bierzo
        • Contact:
        • Principal Investigator:
          • Alberto Bahamonde Carrasco
    • Madrid
      • Alcalá De Henares, Madrid, Spain, 28805
        • Recruiting
        • Hospital Universitario Príncipe de Asturias
        • Contact:
        • Principal Investigator:
          • José María Barbero Allende
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Recruiting
        • Hospital Clinico Universitario Virgen de la Arrixaca
        • Contact:
        • Principal Investigator:
          • Javier Martínez Ros
    • Seville
      • Sevilla, Seville, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocío
        • Contact:
        • Principal Investigator:
          • Jose Manuel Lomas Cabezas
    • Vizcaya
      • Barakaldo, Vizcaya, Spain, 48903

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Short course of antibiotherapy
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)
Combination product: Short course of antibiotherapy
Short duration of authorized antibiotic therapy according to its data sheet in infections associated with osteosynthesis material
Active Comparator: Long course of antibiotherapy
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
Combination product: Long course of antibiotherapy
Long duration of authorized antibiotic therapy according to its data sheet in infections associated with osteosynthesis material

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with clinical cure in the test of cure
Time Frame: 12 months after completion of antimicrobial treatment
A success at the test of cure is the resolution of infection symptoms, the absence of clinical signs and symptoms of infection (persistence of symptoms of infection, relapse of infection after a period without symptoms, or superinfection by a different microorganism) without antibiotic therapy and with C-reactive protein <10 mg/L (unless another cause justifies a higher C-reactive protein value); If the patient dies, when the death was not related to the infection; and no need for chronic suppressive antibiotic therapy to "control" of the infection.
12 months after completion of antimicrobial treatment
Definitive soft tissue coverage at test of cure
Time Frame: 12 months after completion of antimicrobial treatment
Number of patients who present definitive soft tissue coverage at test of cure
12 months after completion of antimicrobial treatment
Radiological healing in the test of cure
Time Frame: 12 months after completion of antimicrobial treatment

Radiological healing is defined as the presence of radiological signs of fracture consolidation (plain radiographic or CT) of the infected bone. Non-union or absence of consolidation of a fractured bone is defined when it has not completely healed within 9 months after osteosynthesis surgery or when it has not shown progression towards fracture callus formation in 3 consecutive months on serial radiographs.

The REBORNE fracture healing scale will be used for a more accurate assessment of fracture healing on radiographs, or CT if necessary.
12 months after completion of antimicrobial treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Performance of an antibiogram to assess the development of antimicrobial resistance
Time Frame: 8 months and 12 months
Standard microbiological techniques will be used to identify microorganisms recovered and to determine antimicrobial susceptibility according to EUCAST recommendation (EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance, Version 2.0, 2017) https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_170711.pdf
8 months and 12 months
Surgical wound culture to assess the development of secondary infections
Time Frame: 8 months and 12 months
To evaluate the appearance of secondary infections during antibiotic treatment that standard microbiological techniques will be used to identify microorganisms recovered and to determine antimicrobial susceptibility according to EUCAST recommendation (EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance, Version 2.0, 2017) https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_170711.pdf
8 months and 12 months
Recurrence rate
Time Frame: 8 months and 12 months
To evaluate the recurrence rate during antibiotic treatment.
8 months and 12 months
Evaluate the need for new surgeries, such as debridement, removal of material, coverage or amputation, through radiological evaluation of fracture union.
Time Frame: Day 28, week 8, week 12, month 6 and month 12.
To evaluate the need for new surgeries through radiological evaluation
Day 28, week 8, week 12, month 6 and month 12.
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.
Time Frame: 6 months and 12 months (visit 6 and 7)
The functional state, normal or reduced, will be evaluated with respect to the situation prior to the fracture. Lower extremity mobility is classified as: walks unassisted; with 1 cane; with 2 canes; with walker; "wander home alone"; not wandering..
6 months and 12 months (visit 6 and 7)
Efficacy of each group of antibiotics
Time Frame: 12 months from the start of antibiotic treatment
Number of days of antibiotic administration
12 months from the start of antibiotic treatment
Evaluation the consumption of health resources
Time Frame: Month 12
Total number and posology of all the antibiotics that have been administered to the patient will be taken into account, in addition to the new surgeries, new microbiological cultures and hospitalizations that have been required.
Month 12
Evaluate the number of patients who have required any of the bone or soft tissue reconstruction strategies.
Time Frame: Month 12
Total number of new surgeries for better bone or soft tissue coverage: number of vacuum therapies (VAC or PICO), total number of grafts or flaps needed by the patient throughout the study.
Month 12
Presentation of adverse events (frequency and severity).
Time Frame: Through study completion (12 months)
Number of adverse events (frequency and severity) that have happened during the study.
Through study completion (12 months)
Clostridium difficile infection
Time Frame: During treatment or 30 days after completion
Number of cases observed during antibiotic treatment or 30 days after completion.
During treatment or 30 days after completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Investigators

  • Principal Investigator: María Dolores del Toro López, Hospital Universitario Virgen Macarena

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 9, 2022

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

April 1, 2026

Study Registration Dates

First Submitted

January 26, 2022

First Submitted That Met QC Criteria

March 15, 2022

First Posted (Actual)

March 24, 2022

Study Record Updates

Last Update Posted (Actual)

August 30, 2024

Last Update Submitted That Met QC Criteria

August 27, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DURATIOM

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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