The RiCOTTA study: Rifampicin Combination Therapy versus Targeted Antibiotic Monotherapy for Infected Joint Prostheses Caused by Staphylococci

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leiden University Medical Center

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

15 May 2023 → ongoing

Decision date (initial)

2023-02-23

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMW (file nr. 10140022110047)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To establish whether targeted monotherapy with clindamycin for PJI in the oral treatment phase is non-inferior to traditional rifampicin/fluoroquinolones combination treatment.

Secondary objectives 2

1. Quality of life, measured with 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 surgical debridement and after 3 months.
2. Adverse events: i. The number of (S)AEs during antimicrobial treatment and follow up (including mortality). ii. The number of switches to a different oral regimen iii. The number of antibiotic side effects (classified by the modified Hartwig and Siegel scale). iv. The number of patients developing Clostridioides difficile infection during treatment. v. The occurrence of rifampicin resistance in bacteria in patients with a microbiologically confirmed failure of treatment.

Conditions and MedDRA coding

prosthetic joint infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. All adult patients, aged 18 years or older AND
2. Diagnosed and hospitalized with hip- or knee prosthetic joint infection caused by Staphylococcus spp AND
3. Treated with DAIR: Debridement, Antibiotics and Implant Retention

Exclusion criteria 12

1. a contra-indication for rifampicin (e.g. a resistant strain or proven allergic reaction or difficult drug-drug-interactions)
2. 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)
3. complicated S. aureus bacteremia or concurrent endocarditis requiring long-term iv antibiotic treatment > 2 weeks
4. treatment failure before the start of oral therapy
5. an unsatisfactory response to initial treatment leading to continuation of intravenous therapy beyond day 21
6. patients with an expected life expectancy <12 months
7. patients with a tumor prosthesis
8. patients receiving chemotherapy for active malignancy in the next 12 months
9. patients who are scheduled in advance for chronic suppressive antibiotic therapy after the initial 12 weeks of antibiotic treatment
10. The patient is unlikely to comply with trial requirements following randomization in the opinion of the investigator
11. Pregnancy
12. Patients who are not able to read or communicate in Dutch or English will be excluded from participating in this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 8

1. Quality of life, measured with EQ-5D-5L questionnaires. This ‘quality of life’ questionnaire will be scored at the time of randomization, at week 6 after surgical debridement and after 3 months.
2. The number of (S)AEs during antimicrobial treatment and follow up (including mortality).
3. The number of switches to a different oral regimen
4. The number of antibiotic side effects (classified by the modified Hartwig and Siegel scale).
5. The number of patients developing Clostridioides difficile infection during treatment.
6. The occurrence of rifampicin resistance in bacteria in patients with a microbiologically confirmed failure of treatment
7. The difference in absolute risks of treatment succes with death unrelated to PJI as a competing event in a per-protocol analysis
8. The difference in absolute risks of treatment success in an intention to treat analysis

Investigational products

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

Test 1

Comparator 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leiden University Medical Center

Sponsor organisation

Leiden University Medical Center

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leiden University Medical Center

Contact name

Henk Scheper

Public contact point

Organisation

Leiden University Medical Center

Contact name

Henk Scheper

Locations

1 EU/EEA country · 21 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 15 files

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

Application history

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