Clinical trial NCT00764114: Comparison of Two Antimicrobial Therapy Duration for Spondylodiscitis
Official title: Comparison of Two Antimicrobial Therapy Duration (6 Weeks Versus 12 Weeks)for Spondylodiscitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Vertebral Osteomyelitis
Keywords: Spondylodiscitis
Duration treatment
Antibiotic
men or women more than 18 years
proved bacterial spondylodiscitis
patient for which is decided a treatment antibiotic
the diagnosis on clinical
Radiological
microbiological criteria
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2008-10-01
Enrollment: 351
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Duration of antimicrobial therapy for spondylodiscitis is not standardized; it could vary from 6 weeks to several months depending on the medical habits. The study hypothesis is that a 6 weeks antimicrobial therapy is not inferior to a 12 weeks.

We run a prospective multi-centric, non inferiority open label trial, randomised in two parallel groups.

The main objective is to compare the efficacy of two durations of antibiotherapy, 6 weeks versus 12 weeks, on the rate of cure in this indication.

The study concerns 400 patients more than 18 years, 70 centres in France are involved.

The duration of the study is 4 years.

Detailed description: In France, incidence of spondylodiscitis is between 1000 and 1500 new cases a year. Micro-organisms mainly in cause are: Staphylococcus aureus, negative coagulase Staphylococcus, Gram negative bacilli and Streptococci; more rarely mycobacteria or Brucella. Actually, optimal duration of antimicrobial therapy is unclear. The rate of cure varies, according to studies, from 90 to 100 % whatever the responsible germ involved. If a 6 weeks antimicrobial therapy duration is not inferior to 12, this would allow to shortening usual antimicrobial therapy duration, and improve tolerance of the treatment, with ecological and economic benefits, following a politics of good use of antibiotics, defined in the French circular n°2002-272 of 02/05/02.

The main objective is to compare two durations of antimicrobial therapy, 6 weeks versus 12 weeks, on the rate of cure of the bacterial spondylodiscitis. Secondary objectives are to compare, according to the duration of treatment antibiotic, 1) Rachidial pain by clinical examination and an analogical visual scale (EVA), 2) Quality of life by the score EQ-5D, 3) Treatment tolerance. 4) Risk factors for failure.

Type of the study is Prospective multi-centric, open label trial, randomised in two parallel groups with direct individual profit.

Antimicrobial therapy is chosen by the physician on charge of the patient according to the germ and to the consensual recommendations.

The study concerns 400 patients.

Inclusion criteria are : men or women more than 18 years, having a proved bacterial spondylodiscitis (not mycobacteria, not fungal nor Brucella), for which an antimicrobial therapy is needed; for the women in age to procreate use of an effective contraception with protected sexual relations and negative pregnancy test (b HCG) is necessary.

Non Inclusion criteria are: infection with no bacteriological identification or mycobacteria, fungal or brucellosis infection, presence of material or recurrence of spondylodiscitis.

Main criterion of evaluation: percentage of success in 1 year defined by the absence of infection : absence of clinical, biological and radiological signs of infection (pain, fever) ; or relapse with the same germ.

This criterion will be estimated beyond the first 6 weeks of treatment antibiotic after the introduction of the treatment and until 1 year after the stop of the treatment. The criteria of the bacteriological diagnosis will be the same.

Design of the study: patients after information consent signed are include and randomised in one arm. They are regularly follow (at 1, 2, 3, 6 and 12 weeks after the beginning of antimicrobial therapy, then at 6 and 12 month after the end of antimicrobial therapy) , with physical examination, biological tests and radiological acts.

The randomisation is centralized, balanced by block, stratifies by centres. (70 centres) The previous duration of the study is of 4 years.

Eligibility criteria: Inclusion Criteria:

* men or women more than 18 years
* proved bacterial spondylodiscitis due to pyogenic germ (no mycobacteria, no fungus or brucella), for which is decided a treatment antibiotic
* diagnosis is based on clinical,radiological and microbiological criteria
* women in age to procreate, use of an effective contraception with protected sexual relations and negative pregnancy test (b HCG).

Exclusion Criteria:

* infection with no bacteriological identification
* infection due to mycobacteria, brucella or fungus
* presence of material
* recurrence of spondylodiscitis
* Patient whose life expectation is 1-year-old subordinate
* pregnant or breast-feeding Woman

Primary outcomes:
measure: Percentage of success in 1 year defined by the absence of infection : absence of clinical, biological and radiological signs of infection (pain, fever) ; or relapse with the same germ.
timeFrame: 1 year after the stop of the treatment.
Secondary outcomes:
measure: 1)Effective antibiotherapy duration
timeFrame: 12 months
measure: 2) Failure rate at 6 month
timeFrame: 6 months
measure: 3)Rachidial pains (clinical examination and analogical visual scale of the pain) at every visit
timeFrame: 6 an 12 month
measure: 4)Quality of life by the score EQ-5D at 6 and 12 month
timeFrame: 6 and 12 month
measure: 5)Observance of the treatment measured at every visit
timeFrame: 6 and 12 month
measure: 6)Appearance of microbial resistances estimated by comparison of antibiogram in case of failure
timeFrame: during 12 months
measure: 7)Antimicrobial therapy tolerance measure at each visit
timeFrame: 6 and 12 month
measure: 8)Identification of risk factors for failure
timeFrame: during 12 months
Other outcomes:
Locations:
city: Garches
country: France
facility: Chu Raymond Poincare
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Louis Bernard, PU-PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Desoutter S, Cottier JP, Ghout I, Issartel B, Dinh A, Martin A, Carlier R, Bernard L; Duration of Treatment for Spondylodiscitis Study Group. Susceptibility Pattern of Microorganisms Isolated by Percutaneous Needle Biopsy in Nonbacteremic Pyogenic Vertebral Osteomyelitis. Antimicrob Agents Chemother. 2015 Dec;59(12):7700-6. doi: 10.1128/AAC.01516-15. Epub 2015 Oct 5.
citation: Zervou FN, Zacharioudakis IM, Mylonakis E. ACP Journal Club. 6 weeks of antibiotics was noninferior to 12 weeks for clinical cure in pyogenic vertebral osteomyelitis. Ann Intern Med. 2015 May 19;162(10):JC7. doi: 10.7326/ACPJC-2015-162-10-007. No abstract available.
citation: Bernard L, Dinh A, Ghout I, Simo D, Zeller V, Issartel B, Le Moing V, Belmatoug N, Lesprit P, Bru JP, Therby A, Bouhour D, Denes E, Debard A, Chirouze C, Fevre K, Dupon M, Aegerter P, Mulleman D; Duration of Treatment for Spondylodiscitis (DTS) study group. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial. Lancet. 2015 Mar 7;385(9971):875-82. doi: 10.1016/S0140-6736(14)61233-2. Epub 2014 Nov 5.