Rifampicin Combination Therapy Versus Monotherapy for Staphylococcal Prosthetic Joint Infection

NCT ID: NCT06172010

Last Updated: 2023-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

316 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-01

Study Completion Date

2028-03-31

Brief Summary

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In this Dutch multicenter clinical trial, patients with a staphylococcal prosthetic joint infection, will, in the oral antibiotic treatment phase, be randomized between clindamycin monotherapy and rifampicin / levofloxacin combination therapy. The clinical endpoint will be treatment success one year after finishing antimicrobial treatment.

Detailed Description

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This is a pragmatic, multicenter, randomized controlled open label trial with a non-inferiority design, comparing the efficacy of rifampicin-based combination antimicrobial therapy versus antimicrobial monotherapy with clindamycin during the oral treatment phase of prosthetic joint infection caused by Staphylococcus spp. The total duration of follow-up will be 15 months from the initial DAIR.

All adult patients, aged 18 years or older, diagnosed and hospitalized with hip- or knee PJI caused by Staphylococcus spp and treated by the DAIR strategy (see Interventions), are eligible for inclusion. The diagnosis of PJI is defined according to the EBJIS 2021 criteria. Exclusion criteria are a contra-indication for rifampicin (due to a resistant strain, a proven allergic reaction, difficult drug-drug-interactions or other contra-indications as listed in the SmPC's of the antibiotics), a contra-indication for levofloxacin and clindamycin and cotrimoxazole and tetracyclines (due to a resistant strain, a proven allergic reaction, difficult drug-drug-interactions or other contra-indications as listed in the SmPC's of the antibiotics), (iii)complicated S. aureus bacteremia or concurrent endocarditis requiring long-term iv antibiotic treatment \> 3 weeks , (iv) an infection for which there are no suitable antibiotic choices to permit randomization between the two arms of the trial (for instance, where organisms are only sensitive to intravenous antibiotics), (v) treatment failure before the start of oral therapy, (vi) more than two separate surgical debridements , (vii)an unsatisfactory response to initial treatment leading to continuation of intravenous therapy beyond day 21, (viii) patients with an expected life expectancy \<12 months, (ix) patients with a tumor prosthesis , (x) patients receiving chemotherapy for active malignancy in the next 12 months, (xi) patients who are scheduled in advance for chronic suppressive antibiotic therapy after the initial 12 weeks of antibiotic treatment, (xii) The patient is unlikely to comply with trial requirements following randomization in the opinion of the investigator, (xiii) Pregnancy or breastfeeding, (xiv) Patients who are not able to read or communicate in Dutch or English will be excluded from participating in this study.

The main trial endpoint is treatment success 15 months after DAIR (=1 year after finishing antibiotic treatment). Treatment success will be defined as absence of all of the following:

(I) Infection related re-surgery of the initially affected prosthetic joint (II) New antibiotic treatment for suspected or proven infection of the index joint.

(III) Ongoing use of antibiotics for the index joint at the end of follow-up. (IV) Death

Secondary outcomes are (a) Quality of life, measured with the 5-level EQ-5D version (EQ-5D-5L) questionnaires. The EQ-5D-5L is a standardized and validated measure of health status developed by the EuroQol Group to provide a comprehensive generic measure of health for clinical and economic appraisal. This 'quality of life' questionnaire will be scored at the time of randomization, at week 6 after the initial surgical debridement and after 3 months.

(b) Adverse events. The number of SAEs during antimicrobial treatment and follow up ii. The number of switches to a different oral regimen, iii. The number of antibiotic associated AEs (classified by the modified Hartwig and Siegel scale). (c) The number of patients developing Clostridioides difficile infection during treatment. (d) The occurrence of rifampicin resistance in bacteria in patients with a microbiologically confirmed failure of treatment.

Conditions

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Prosthetic-joint Infection Infection Hip Infection; Knee, Joint

Keywords

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rifampicin clindamycin levofloxacin prosthetic joint infection antimicrobial treatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

randomized controlled open label trial with a non-inferiority design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Oral rifampicin-based combination therapy

rifampicin 450mg BID + levofloxacin 500mg BID in the oral treatment phase with a total duration of antibiotics of 12 weeks

Group Type ACTIVE_COMPARATOR

Rifampicin and levofloxacin

Intervention Type DRUG

antimicrobial treatment in oral treatment phase of staphylococcal prosthetic joint infection

Oral monotherapy with clindamycin

clindamycin 600mg TID in the oral treatment phase with a total duration of antibiotics of 12 weeks

Group Type EXPERIMENTAL

Clindamycin

Intervention Type DRUG

antimicrobial treatment in oral treatment phase of staphylococcal prosthetic joint infection

Interventions

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Clindamycin

antimicrobial treatment in oral treatment phase of staphylococcal prosthetic joint infection

Intervention Type DRUG

Rifampicin and levofloxacin

antimicrobial treatment in oral treatment phase of staphylococcal prosthetic joint infection

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* \>18 years of age
* Confirmed staphylococcal prosthetic hip or knee joint infection according to the current EBJIS 2021 definition of PJI
* The causative agents are (or include) S. aureus or and/or Coagulase-negative staphylococci (CNS)
* Treatment is according to the DAIR-procedure

Exclusion Criteria

(i) a contra-indication for rifampicin (e.g. a resistant strain or proven allergic reaction or difficult drug-drug-interactions) (ii) complicated S. aureus bacteremia or concurrent endocarditis requiring long-term iv antibiotic treatment \> 2 weeks (iii) An infection for which there are no suitable antibiotic choices to permit Randomization between the two arms of the trial (for instance, where organisms are only sensitive to intravenous antibiotics) (iv) treatment failure before the start of oral therapy, (v) an unsatisfactory response to initial treatment leading to continuation of intravenous therapy beyond day 21, (vi) patients with an expected life expectancy \<12 months, (vii) patients with a tumor prosthesis (viii) patients receiving chemotherapy for active malignancy in the next 12 months (ix) patients who are scheduled in advance for chronic suppressive antibiotic therapy for \>12 months, (x) The patient is unlikely to comply with trial requirements following Randomization in the opinion of the investigator (xi) Pregnancy (xii) Patients who are not able to read or communicate in Dutch or English will be excluded from participating in this study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Medical Center Groningen

OTHER

Sponsor Role collaborator

Onze Lieve Vrouwe Gasthuis

OTHER

Sponsor Role collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role collaborator

Frisius Medisch Centrum

OTHER

Sponsor Role collaborator

Isala

OTHER

Sponsor Role collaborator

Martini Hospital Groningen

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role collaborator

Sint Maartenskliniek

OTHER

Sponsor Role collaborator

Elisabeth-TweeSteden Ziekenhuis

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role collaborator

Alrijne Hospital

OTHER

Sponsor Role collaborator

Spaarne Gasthuis

OTHER

Sponsor Role collaborator

Reinier Haga Orthopedisch Centrum

OTHER

Sponsor Role collaborator

Tergooi Hospital

OTHER

Sponsor Role collaborator

Rijnstate Hospital

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Mark de Boer MD PhD

Prof dr MGJ de Boer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Henk Scheper, MD

Role: STUDY_DIRECTOR

LUMC

Locations

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LUMC

Leiden, Zuid Hollans, Netherlands

Site Status RECRUITING

Amsterdam UMC

Amsterdam, , Netherlands

Site Status RECRUITING

OLVG

Amsterdam, , Netherlands

Site Status RECRUITING

Martini ziekenhuis

Groningen, , Netherlands

Site Status NOT_YET_RECRUITING

UMCG

Groningen, , Netherlands

Site Status RECRUITING

Spaarne gasthuis

Hoofddorp, , Netherlands

Site Status RECRUITING

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Site Status RECRUITING

Alrijne Ziekenhuis

Leiderdorp, , Netherlands

Site Status RECRUITING

Radboud UMC

Nijmegen, , Netherlands

Site Status RECRUITING

Sint maartenskliniek

Nijmegen, , Netherlands

Site Status RECRUITING

Erasmus MC

Rotterdam, , Netherlands

Site Status NOT_YET_RECRUITING

Elisabeth Tweesteden Ziekenhus

Tilburg, , Netherlands

Site Status RECRUITING

Stichting Isala Klinieken

Zwolle, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Henk Scheper, MD

Role: CONTACT

Phone: 071-5299239

Email: [email protected]

Mark De Boer, MD PhD

Role: CONTACT

Phone: 071-5269111

Email: [email protected]

Facility Contacts

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Henk Scheper, MD PhD

Role: primary

Edgar Peters

Role: primary

Rudolf Poolman

Role: primary

Bas ten Have

Role: primary

Marjan Wouthuyzen-Bakker

Role: primary

Peter Nolte

Role: primary

Wierd Zijlstra

Role: primary

Rachid Mahdad

Role: primary

Wim Rijnen

Role: primary

Karn Veerman

Role: primary

Koen Bos

Role: primary

Olav van der Jagt

Role: primary

Jolanda Lammers

Role: primary

References

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Scheper H, Gerritsen LM, Pijls BG, Van Asten SA, Visser LG, De Boer MGJ. Outcome of Debridement, Antibiotics, and Implant Retention for Staphylococcal Hip and Knee Prosthetic Joint Infections, Focused on Rifampicin Use: A Systematic Review and Meta-Analysis. Open Forum Infect Dis. 2021 Jul 1;8(7):ofab298. doi: 10.1093/ofid/ofab298. eCollection 2021 Jul.

Reference Type RESULT
PMID: 34258321 (View on PubMed)

Related Links

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http://www.protheseinfectie.nl

Website with information for patients and physicians about RiCOTTA study

Other Identifiers

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2022-501620-26-00

Identifier Type: -

Identifier Source: org_study_id