NCT02599493

Brief Summary

Rifampicin is an antibiotic usually required to treat susceptible Staphylococcus spp. osteo-articular infections, most frequently in association with a fluoroquinolone when the strain is susceptible to both agents. It is the reference treatment for orthopedic infections with implanted material. For tuberculosis treatment the dosage of 10 mg/kg/j is usually prescribed, while in the treatment of Staphylococcus spp. infections the highest dosage of 20 mg/kg/j is proposed by French experts' recommendations from 2009. However, there is little evidence in the literature, which could set out arguments to choose the best dosage of rifampicin, which may vary from 5 to 20 mg/kg. The issue with rifampicin is side effects, in particular with long-term treatment. Many side effects may occur in 10 to 20% of patients and sometimes leads to dosage reduction or treatment interruption. In the literature, there is little evidence that higher rifampicin dosage is associated with higher frequency of adverse effects. Depending on the nature of the toxicity, one could say that hypersensitivity could be independent from dosage, when digestive disorders may be related. Plasmatic concentrations studies have not given strong arguments to link higher rifampicin dosages with side effects occurrence rates. After oral absorption, plasmatic peak occurs after two to five hours and varies among individuals but also in the same patient overtime. This particular pharmacokinetic profile could explain discrepancy in adverse events (AEs) frequencies.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
544

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jan 2016

Longer than P75 for phase_4

Geographic Reach
1 country

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 3, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 6, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

August 23, 2021

Status Verified

August 1, 2021

Enrollment Period

4.9 years

First QC Date

November 3, 2015

Last Update Submit

August 20, 2021

Conditions

Osteoarticular Infection

Outcome Measures

Primary Outcomes (1)

  • Proven failure

    The rate of proven failure between the two groups, 12 months after the end of antibiotics. The proven failure is defined as a documented bacteriological failure, with the same Staphylococcus spp. strain isolated before the onset of antibiotics and at diagnosis of failure.

    12 months

Secondary Outcomes (8)

  • Possible failure

    12 months

  • Adverse events

    12 weeks

  • Dose modification

    12 weeks

  • Failure risk factors

    12 months

  • Global health costs

    12 weeks

  • +3 more secondary outcomes

Study Arms (2)

Low dose

EXPERIMENTAL

Patients will be randomly assigned to low dosage (10 mg/kg/j) rifampicin group. Rifampicin treatment will be prescribed in association with another antibiotic chosen by investigator according to the antibiogram results. Association with fluoroquinolones is the first choice combination, if it is possible. The global antibiotic treatment duration depends on the investigator's choice.

Drug: Rifampicin

High dose

ACTIVE COMPARATOR

Patients will be randomly assigned to high dosage (20 mg/kg/j) rifampicin group. Rifampicin treatment will be prescribed in association with another antibiotic chosen by investigator according to the antibiogram results. Association with fluoroquinolones is the first choice combination, if it is possible. The global antibiotic treatment duration depends on the investigator's choice.

Drug: Rifampicin

Interventions

RifampicinDRUG

Patients will be randomly assigned to low dosage (10 mg/kg/j) rifampicin group or high dosage (20 mg/kg/j) rifampicin group. Rifampicin treatment will be prescribed in association with another antibiotic chosen by investigator according to the antibiogram results. Association with fluoroquinolones is the first choice combination, if it is possible. The global antibiotic treatment duration depends on the investigator's choice.

Also known as: RIMACTAN
High doseLow dose

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult patients (over 18 years old) who gave their signed inform consent,
  • Who present an osteo-articular infection with susceptible Staphylococcus spp.,
  • To whom a rifampicin based regimen is prescribed, in association with another antibiotic, for at least 14 days,
  • Patients covered by Health Insurance.

You may not qualify if:

  • Patients weighing less than 45 kg or more than 150 kg,
  • Patients with active TB (whatever its localization),
  • Patients needing the imperative use of a treatment presenting a contraindication for concomitant use in the SPC of Rimactan®
  • Patients with a known and documented rifampicin allergy or severe rifampicin intolerance,
  • Patients with galactose intolerance, total lactase deficiency or glucose or galactose malabsorption syndrome, or any other contraindication to the administration of Rimactan® listed in the SPC for Rimactan®
  • Pregnant or breastfeeding woman,
  • Adults legally protected (under judicial protection, guardianship or supervision), persons deprived of their liberty,
  • Patients participating in another interventional clinical trial (biomedical trial or standard care clinical trial).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Angers university hospital

Angers, 49933, France

Location

Bordeaux university hospital

Bordeaux, 33076, France

Location

Brest university hospital

Brest, 29609, France

Location

Caen university hospital

Caen, 14033, France

Location

La Roche sur Yon hospital

La Roche-sur-Yon, 85925, France

Location

Lorient hospital

Lorient, 56322, France

Location

Clinique du Parc et Hôpital Jean Mermoz

Lyon, 69100, France

Location

Nantes university hospital

Nantes, 44093, France

Location

Pau hospital

Pau, 64046, France

Location

Poitiers university hospital

Poitiers, 86000, France

Location

Rennes university hospital

Rennes, 35000, France

Location

Saint-Brieuc hospital

Saint-Brieuc, 22027, France

Location

Saint-Malo hospital

St-Malo, 35400, France

Location

Toulouse university hospital

Toulouse, 35059, France

Location

Tours university hospital

Tours, 37044, France

Location

Vannes hospital

Vannes, 56017, France

Location

MeSH Terms

Interventions

Rifampin

Intervention Hierarchy (Ancestors)

RifamycinsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic Compounds

Study Officials

  • Cédric ARVIEUX, MD

    Rennes University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 3, 2015

First Posted

November 6, 2015

Study Start

January 1, 2016

Primary Completion

December 1, 2020

Study Completion

December 1, 2020

Last Updated

August 23, 2021

Record last verified: 2021-08

Locations

FR(16)