Impact of rifampicin in treatment outcome of Cutibacterium spp. prosthetic joint infections - RIFACute

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nice

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

27 Nov 2023 → ongoing

Decision date (initial)

2023-05-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-502974-18-00

ClinicalTrials.gov

NCT05902221

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Two main objectives will be analyzed according to the hierarchical sequential procedure (closed-testing procedure) in the following order:
1.To study the safety of rifampicin during C. spp. prosthetic joint infection treatment
2.To study the efficacy of rifampicin during C. spp. prosthetic joint infection treatment

Secondary objectives 2

1. To study rifampicin efficacy according to its companion
2. 2. To study clinical cure of monomicrobial C. spp. prosthetic joint infections assessed 12 months after antibiotic cessation (M15), related to the use of Rifampicin in combination with one another antibiotic treatment (dual antibiotic treatment including rifampicin) versus a single antibiotic treatment (i.e. without rifampicin).

Conditions and MedDRA coding

C. spp. prosthetic joint infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. • Age: > or = 18 years old
2. • Monomicrobial, rifampicin susceptible Cutibacterium spp. total knee arthroplasty (TKA) or hip arthroplasty (total, THA or hemiarthroplasty, HH) or shoulder arthroplasty (total, TSA or hemiarthroplasty, SH) infection treated surgically with single-stage or two-stage revision (complete or single-pole replacement are authorised); for late infections (more than 4 weeks after surgery) or with DAIR (less than 4 weeks after surgery)
3. • Detection of C. spp. on two distinct per-operative samples collected during the single-stage or the two-stage revision;. At least one isolation by conventional culture method is required. 16s rDNA sequencing and metagenomic sequencing techniques can be used to define one sample or more as positive for C. acnes.
4. • Based on the antimicrobial susceptibility test of the C. spp. and the medical history of the patient, the PJI can be treated with amoxicillin or moxifloxacin

Exclusion criteria 9

1. • Contraindication to Rifampicin (included ongoing treatment contraindicated with rifampicin)
2. • Disease-modifying treatment incompatible with the inducer effect of rifampicin
3. • Liver cirrhosis
4. • Pregnancy: a pregnancy urinary test will be performed on all women of childbearing age. The results will be sent to the patient by the doctor of their choice
5. • Porphyria
6. • Renal insufficiency with GFR < 30ml/min/1.73 m² (MDRD)
7. Contraindication to Amoxicillin AND moxifloxacin (included ongoing treatment contraindicated with these medicines)
8. Rifampicin prior to randomization for current episode of arthroplasty infection;
9. Management not planned with a curative aim, suppressive antibiotic treatment is considered.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Rate of C. spp. prosthetic joint infections management failure defined by: RELAPSE or NEW INFECTION or EARLY FAILURE
2. 2. Rate of adverse event linked to rifampicin, classified according to the CTCAE 5.0. The adverse events will be described by frequency and grade, throughout the treatment, with the maximum grade over all cycles used as the summary measure for each patient.

Secondary endpoints 3

1. 1. Rate of C. spp. prosthetic joint infections probable failure suspected in case of specific clinical signs (fistula) and/or inflammatory synovial fluid without microbiological positive results and/or histopathological results after revision without microbiological positive results during the 24 months of follow-up
2. 2. Rate of C. spp. prosthetic joint infections management failure (as defined for the primary endpoint) during the 24 months of follow-up according to the two usable companions in the trial (amoxicillin and moxifloxacin).
3. Rate of C. spp. prosthetic joint infections management failure (as defined for the primary end-point) during the 12 months of follow-up

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nice

Sponsor organisation

Centre Hospitalier Universitaire De Nice

Address

4 Avenue Reine Victoria

City

Nice

Postcode

06000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nice

Contact name

Johan COURJON

Public contact point

Organisation

Centre Hospitalier Universitaire De Nice

Contact name

Maeva GODEMERT

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications