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

NCT05294796 | Recruiting Phase 3 DMC

• 1 other identifier: DURATIOM
• Study Type: interventional
• Target: 364
• Locations: 1 country
• Sites: 29

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.

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

Outcome Measures

Primary Outcomes (3)

• Number of participants with clinical cure in the test of cure

  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

• Radiological healing in the test of cure

  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

• Definitive soft tissue coverage at test of cure

  Number of patients who present definitive soft tissue coverage at test of cure

  12 months after completion of antimicrobial treatment

Secondary Outcomes (10)

• Efficacy of each group of antibiotics

  12 months from the start of antibiotic treatment

• Performance of an antibiogram to assess the development of antimicrobial resistance

  8 months and 12 months

• Surgical wound culture to assess the development of secondary infections

  8 months and 12 months

• Recurrence rate

  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.

  Day 28, week 8, week 12, month 6 and month 12.

Study Arms (2)

Short course of antibiotherapy

ACTIVE COMPARATOR

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

Long course of antibiotherapy

ACTIVE COMPARATOR

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

Interventions

Short course of antibiotherapy COMBINATION_PRODUCT

Short duration of authorized antibiotic therapy according to its data sheet in infections associated with osteosynthesis material

Short course of antibiotherapy

Long course of antibiotherapy COMBINATION_PRODUCT

Long duration of authorized antibiotic therapy according to its data sheet in infections associated with osteosynthesis material

Long course of antibiotherapy

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead

Study Sites (29)

Hospital Universitario Son Espases

Palma, Balearic Islands, 07120, Spain

RECRUITING

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

Hospital Universitario Parc Taulí

Sabadell, Barcelona, 08208, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital Universitario Jerez de la Frontera

Jerez de la Frontera, Cádiz, 11407, Spain

RECRUITING

Hospital San Pedro

Logroño, La Rioja, 26006, Spain

RECRUITING

Hospital Universitario El Bierzo

Ponferrada, León, 24404, Spain

RECRUITING

Hospital Universitario Príncipe de Asturias

Alcalá de Henares, Madrid, 28805, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, Seville, 41013, Spain

RECRUITING

Hospital Universitario de Cruces

Barakaldo, Vizcaya, 48903, Spain

RECRUITING

Hospital del Mar

Barcelona, 08003, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

RECRUITING

Hospital Universitario Puerto Real

Cadiz, 11510, Spain

RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

RECRUITING

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

TERMINATED

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Hospital Universitario Costa del Sol

Málaga, 29603, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

Hospital Universitario Virgen de Valme

Seville, 41014, Spain

RECRUITING

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

RECRUITING

Related Publications (1)

• Garrigos C, Rosso-Fernandez CM, Borreguero I, Rodriguez P, Garcia-Albea R, Bravo-Ferrer JM, Rodriguez-Bano J, Del Toro MD; DURATIOM team. Efficacy and safety of different antimicrobial DURATions for the treatment of Infections associated with Osteosynthesis Material implanted after long bone fractures (DURATIOM): Protocol for a randomized, pragmatic trial. PLoS One. 2023 May 22;18(5):e0286094. doi: 10.1371/journal.pone.0286094. eCollection 2023.

  PMID: 37216357 DERIVED

MeSH Terms

Conditions

Infections

Study Officials

• María Dolores del Toro López

  Hospital Universitario Virgen Macarena

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clara Rosso Fernández

CONTACT

955012144; clara.rosso.sspa@juntadeandalucia.es

Irene Borreguero Borreguero

CONTACT

955007609; irene.borreguero@juntadeandalucia.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: March 24, 2022
• Study Start: August 9, 2022
• Primary Completion: October 1, 2024
• Study Completion: April 1, 2026
• Last Updated: August 30, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (29)