Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02971657
Other study ID # 2011-02
Secondary ID
Status Completed
Phase N/A
First received November 21, 2016
Last updated November 23, 2016
Start date November 2011
Est. completion date March 2015

Study information

Verified date November 2016
Source BG Unfallklinik
Contact n/a
Is FDA regulated No
Health authority Germany: Ethics Commission
Study type Observational

Clinical Trial Summary

This was a prospective study performed between November 2011 and September 2013. Patients with a confirmed S. aureus infection after fracture fixation or prosthetic joint infection were included. Exclusion criteria included infections involving external fixation pins, infections without any implanted hardware and culture positive patients not displaying any clinical sign of infection. The following surgical parameters were documented: affected bone or joint; type of implant; time between implantation of the device and onset of symptoms. Personal characteristics and patients`health status were also documented. Any revision surgeries involving the site of interest and all isolated pathogens were recorded throughout the course of treatment and follow-up.

A follow up examination was performed an average of 23 months after discharge. Primary outcome at follow up was cure. Cure was defined by the authors as: missing local (at site of interest) or systemic signs of infection, terminated surgical and systemic therapy and restoration of joint or limb function.

At the first surgical procedure after enrolment, at least four deep bone biopsies were taken from the interface between implant and affected bone. Identification and antibiotic susceptibility testing of all growth was performed. Multi-drug-resistance (MDR) was defined according to the definitions of the European Committee of Antimicrobial Susceptibility Testing (EUCAST). Biofilm formation was analysed and quantified in microtitre plate assays according to protocol of Stepanovic et al.(see references).


Description:

This was a prospective study performed between November 2011 and September 2013. All patients provided informed written consent prior to inclusion in the study. Inclusion criteria were deep S. aureus infections after fracture fixation or prosthetic joint surgery. Fracture fixation infections includes fractures involving the long bones as well as the pelvis and the spine. Bacterial growth at the site of interest in combination with either pseudarthrosis, implant-loosening/failure or local and systemic signs of surgical site infection were required for inclusion. Exclusion criteria included infections involving external fixation pins, infections without any implanted hardware and culture positive patients not displaying any clinical sign of infection.

Upon entry into the study, the following surgical parameters were documented: affected bone or joint; type of implant; time between implantation of the device and onset of symptoms. Personal characteristics were also documented and included: gender; age; body mass index (BMI); smoker/non-smoker; overall medical condition (Charlson comorbidity index); and chronic immunosuppressive conditions (Diabetes mellitus, chronic alcoholism, Child`s class C cirrhosis, neoplasia, transplantation, AIDS and steroid medication). Any revision surgeries involving the site of interest and all isolated pathogens were recorded throughout the course of treatment and follow-up.

A follow up examination was performed an average of 23 months after discharge. Primary outcome at follow up was cure. Cure was defined by the authors as: missing local (at site of interest) or systemic signs of infection and terminated surgical and systemic therapy.

At the first surgical procedure after enrolment, at least four deep bone biopsies were taken from the interface between implant and affected bone. The tissue samples were placed in a sterile container with thioglycollate liquid medium (bioMérieux, Hazelwood, MO, USA). The samples were cultured for ten days at 37°C and examined each day macroscopically. Any growth was inoculated onto a blood agar plate (bioMérieux, Hazelwood, MO, USA) for further growth and subsequent identification. In all cases, additional swabs and soft tissue samples may have been taken as per clinical routine, however, only samples adjacent to the implant were used for diagnosis in this study.

Identification and antibiotic susceptibility testing of all growth was performed using a Vitek2 (bioMerieux Vitek Inc, Hazelwood, MO, USA). Multi-drug-resistance (MDR) was defined according to the definitions of the European Committee of Antimicrobial Susceptibility Testing (EUCAST). Oxacillin resistance was used as an indicator for methicillin resistant S. aureus (MRSA).

Biofilm formation was analysed and quantified in microtitre plate assays according to the well-established protocol of Stepanovic et al.(see references).

The key variables with regards to bacterial phenotype were: biofilm formation; methicillin resistance;multidrug resistance;staphyloxanthin production and hemolysis. The primary outcome measure was whether the infection was "cured" or not. Primary outcome parameters were calculated as a function of all patients for whom data was complete. Statistical comparison was restricted to the lower extremity cohort since the other patients are not scored for many of the functional outcome measures and as such incomplete.

Univariate logistic regression models were used to determine the influence of each prognostic factor (obesity, smoking, diabetes mellitus, chronic immune suppression, open fracture (initially), early onset infection, biofilm formation, methicillin resistance, MDR and Charlson comorbidity index) on cure. P-values <0.05 were considered significant. Statistical analyses were performed using SAS software (Version 9.2; Cary, NC, USA).


Recruitment information / eligibility

Status Completed
Enrollment 126
Est. completion date March 2015
Est. primary completion date February 2015
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Infections after fracture fixation or prosthetic joint surgery

- Affected bone or joint: Long bones of the lower and upper extremity

- Bacterial growth of S. aureus at the site of interest

- Written consent

- Age: 18 and older

Exclusion Criteria:

- no prove of bacterial growth at site of interest

- missing consent

- infections involving external fixation pins, infections without any implanted hardware.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective


Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
BG Unfallklinik AO Research Institute Davos/ Switzerland

References & Publications (2)

Post V, Wahl P, Uçkay I, Ochsner P, Zimmerli W, Corvec S, Loiez C, Richards RG, Moriarty TF. Phenotypic and genotypic characterisation of Staphylococcus aureus causing musculoskeletal infections. Int J Med Microbiol. 2014 Jul;304(5-6):565-76. doi: 10.1016/j.ijmm.2014.03.003. — View Citation

Stepanovic S, Vukovic D, Hola V, Di Bonaventura G, Djukic S, Cirkovic I, Ruzicka F. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS. 2007 Aug;115(8):891-9. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Cure Cure was defined by the authors as: missing local (at site of interest) or systemic signs of infection and terminated surgical and systemic antibiotic therapy. All Parameters had to be positive to fulfill the outcome parameter "cure".If one of the mentioned parameters was negative, outcome was defined as "not cured". Local signs of infection were defined as the appearance of: redness, tenderness, swelling or persisting wound drainage. 23 months No
See also
  Status Clinical Trial Phase
Completed NCT01447407 - Effect of Adjuvant & Route of Administration on Safety & Immunogenicity of NDV-3 Vaccine Phase 1
Recruiting NCT00518076 - Staphylococcus Aureus Carriers Students Nursing Oxacillin Resistant N/A
Completed NCT01324440 - Safety, Tolerability, and Immunogenicity of a Single Dose of Merck 0657nI Staphylococcus Aureus Vaccine With or Without Merck Aluminum Adjuvant (V710-002) Phase 1
Completed NCT00501150 - Oral Antibiotic Treatment at Home Instead of Intravenous Treatment in Hospital for Resistant Gram Positive Infections N/A
Completed NCT00071214 - Study to Evaluate the Effectiveness of StaphVAX in Adults on Hemodialysis Phase 3
Completed NCT00063089 - Safety and Behavior of S. Aureus Immune Globulin Intravenous(Human), [Altastaph] in Patients With S. Aureus Bacteremia and Continuing Fever Phase 1/Phase 2
Completed NCT00175370 - Vancomycin Study: Treatment of Catheter Related Bloodstream Infection Caused by Coagulase Negative Staphylococcus N/A
Recruiting NCT03456544 - Vancomycin-Associated Acute Kidney Injury: A Cross-Sectional Study From a Multi- Center in China
Completed NCT02557568 - Evaluation of an Algorithm for Identifying Persistent Nasal Staphylococcus Aureus Carriage in a Cohort of Healthy Volunteers and Patients Regularly Monitored at the CHU of Saint-Etienne N/A
Terminated NCT01196169 - Daptomycin Use for Antimicrobial Prophylaxis in Methicillin Resistant Staphylococcus Aureus (MRSA) Colonized Adult Patients Undergoing Primary Elective Hip, Knee, or Shoulder Arthroplasty Phase 4
Completed NCT01431326 - Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
Completed NCT02640937 - Biofilm Formation in Staphylococcus Epidermidis Associated Implant Infections N/A
Completed NCT00303069 - V710 First-In-Man (FIM) Study (V710-001) Phase 1
Completed NCT00156377 - Prophylaxis With Intranasal Mupirocin for Prevention of S. Aureus Infections Phase 4
Completed NCT00631566 - Prospective Study of Methicillin-Resistant Staphylococcus Aureus (MRSA) Among HIV-Infected Persons N/A
Completed NCT00113191 - Safety and Efficacy of Veronate® Versus Placebo in Preventing Nosocomial Staphylococcal Sepsis in Premature Infants N/A
Completed NCT02782078 - Pharmacological Interaction of Rifampicin on Clindamycin in Staphylococcic Osteoarticular Infections N/A
Completed NCT00859677 - Immunologic Predisposition of HIV Patients to Develop Methicillin-Resistant Staphylococcus Aureus (MRSA) Colonization and Infection
Completed NCT00211900 - Evaluation of Manufacturing Lot of StaphVAX Phase 3
Completed NCT02492958 - SA4Ag Safety, Tolerability, and Immunogenicity Study in Japanese Adults Phase 2