Tedizolid Prolonged Treatment for Prosthetic Joint Infections (TEDIZOAM)

September 6, 2021 updated by: Tourcoing Hospital

Prospective Cohort Study on Patients With Tedizolid Prolonged Therapy for Orthopedic Device Infections

Pilot study the aim of which is to obtain reliable data on the tolerance, compliance and efficacy of Tedizolid used as prolonged (≥ 6 weeks) monotherapy or in combination therapy for the treatment of patients with orthopedic device infections due to Gram positive cocci.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background: The antibiotic treatment of patients with orthopedic device infections (e.g. prosthetic joint and osteosynthesis) is limited by the tolerance of prolonged administration of antibiotics and the high level of antibiotic resistance of some pathogens.

The prolonged intravenous administration of antibiotics exposes the patients to the occurrence of adverse events and it is generally recommended to favor oral treatment provided high oral bioavailable agents can be used with regard to the patient's characteristics and the antibiotic susceptibility profile of the pathogens.

Gram positive cocci especially coagulase negative staphylococci (CoNS) are predominant bacteria responsible for orthopedic device infections. The use of the oxazolidinone agent Linezolid in these settings has been validated by some studies in particular in combination with Rifampin but both hematologic, neurologic and metabolic potential toxicity limits treatment durations of more than two to three weeks. The risk of drug-drug interaction with any product having a mono-amine-oxydase inhibitor (MAOI) activity is another limiting problem with Linezolid use.

In addition, the wide use of Linezolid has resulted in the emergence of CoNS carrying cfr genes responsible for high levels of Linezolid resistance. This is unfortunate as in many cases there is almost no other alternative for the oral treatment of orthopedic device infections due to these strains.

Tedizolid intrinsic properties may improve the oxazolidinone treatment long term safety. Plus tedizolid should be active on CoNS strains resistant to linezolid.

Objectives: Obtain reliable data on the tolerance, compliance and efficacy of Tedizolid used as prolonged (≥ 6 weeks) monotherapy or in combination therapy for the treatment of patients with orthopedic device infections due to Gram positive cocci.

Hypothesis: As no data are currently available on long term safety of Tedizolid treatment, the investigators will compare the results of the present study regarding tolerance and efficacy with those of a historical cohort of comparable patients from our cohorts treated with Linezolid monotherapy or combination therapy for equivalent indications (data published in Journal of Antimicrobial Chemotherapy Legout L et al..2010).

Study Design: Prospective multicenter cohort study.

The objectives of the study are :

(i) to assess the tolerance of TEDIZOLID determined by the proportion of patients who experienced any adverse event attributable to TEDIZOLID during treatment and during 6 weeks after the antibiotic treatment, and (ii) to assess the efficacy of TEDIZOLID as single agent treatment or combined therapy for orthopedic infections due to TEDIZOLID susceptible bacteria determined by the proportion of patient with remission of the infection (i.e. absence of any local and systemic sign of infection in relation with the initial infection, any surgery for an infectious reason at the initial site or death related to the initial infection) determined one year after the end of the antibiotic treatment.

Microbiologic data from failure cases will be recorded in order to assess the presence of Tedizolid-resistant strains, relapsing infections, or superinfection.

Treatment: Tedizolid 200 mg once a day, administered orally for the entire treatment will be prescribed in patients after the definite culture results of peroperative samples will be available.

Daily doses of the antibiotics associated with tedizolid will be at the discretion of the clinician and will have to follow the institutional therapeutical protocols.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • France
      • Boulogne-Billancourt, France, 92380
        • Hôpital Ambroise Paré
      • Lyon, France, 69004
        • Hôpital de la Croix Rousse

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient at least 18 years;
  • Orthopedic device infection defined according to the French recommendations published in 2009 (Med Mal Infect 2009; 39:745-774) for which TEDIZOLID treatment is proposed according to the investigator's decision;
  • Bacterial documentation of the infection will only be based on the results of reliable samples such as joint aspiration and peroperative samples.
  • Requiring TEDIZOLID administration as a single antibiotic therapy or in combination therapy including another agent with proven activity against the involved pathogen(s);
  • No contraindication to TEDIZOLID;
  • Provide a signed informed consent for the trial.

Exclusion Criteria:

  • pregnant women or of childbearing age without contraception, breastfeeding,
  • intolerance to TEDIZOLID;
  • allergy to LINEZOLID;
  • bactéria non susceptible to TEDIZOLID;
  • patient with uncertainty regarding the possibility to achieve one-year follow-up after the end of treatment.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tedizolid Phosphate 200 MG [Sivextro]
All included patients will receive prolonged (>= 6 weeks) tedizolid treatment given orally.
Drug: Tedizolid Phosphate 200 MG [Sivextro]
Antibiotic treatment (monotherapy or combination) targeting bacteria cultured from per operative samples.
Other Names:
  • levofloxacin
  • rifampin
  • ofloxacin
  • fusidic acid
  • clindamycin
  • teicoplanin
  • ciprofloxacin
  • trimethoprim-sulfamethoxazole
  • doxycycline
  • minocycline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone marrow toxicity
Time Frame: From date of inclusion until 12 months after the end of treatment
assessed on the values of hemoglobin, leucocytes, neutrophils and platelets counts, will be collected to determine the number of adverse event likely to be related to tedizolid treatment.
From date of inclusion until 12 months after the end of treatment
Peripheral neuropathy
Time Frame: From date of inclusion until 12 months after the end of treatment
Paresthesia, dysesthesia, hypoesthesia, allodynia (confirmed by EMG examination), will be collected to determine the number of adverse event likely to be related to tedizolid treatment.
From date of inclusion until 12 months after the end of treatment
Metabolic acidosis
Time Frame: From date of inclusion until 12 months after the end of treatment
dyspnea of unknown origin ; pH < 7.35 ; [ HCO3- ] < 22 mmol/L ; paCO2 < 45 mmHg ; lactates > 2 mmol/L, will be collected to determine the number of adverse event likely to be related to tedizolid treatment.
From date of inclusion until 12 months after the end of treatment
Serotoninergic syndrome
Time Frame: From date of inclusion until 12 months after the end of treatment
will be collected to determine the number of adverse event likely to be related to tedizolid treatment.
From date of inclusion until 12 months after the end of treatment
Retrobulbar optic nevritis
Time Frame: From date of inclusion until 12 months after the end of treatment
will be collected to determine the number of adverse event likely to be related to tedizolid treatment.
From date of inclusion until 12 months after the end of treatment

Collaborators and Investigators

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

Sponsor

Tourcoing Hospital

Collaborators

Eric SENNEVILLE M.D. Ph.D.

Investigators

  • Study Chair: Eric SENNEVILLE, M.D. Ph. D., G. Dron Hospital, Tourcoing, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 28, 2018

Primary Completion (Actual)

October 22, 2020

Study Completion (Actual)

August 22, 2021

Study Registration Dates

First Submitted

October 24, 2017

First Submitted That Met QC Criteria

December 18, 2017

First Posted (Actual)

December 19, 2017

Study Record Updates

Last Update Posted (Actual)

September 8, 2021

Last Update Submitted That Met QC Criteria

September 6, 2021

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-001238-24

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

product manufactured in and exported from the U.S.

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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