search
Back to results

Comparison Between Two Durations of Antibiotherapy for Non-surgically-treated Diabetic Foot Osteomyelitis (CHRONOS-2) (CHRONOS-2)

Primary Purpose

Osteomyelitis - Foot

Status
Not yet recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Reduction in the duration of antibiotic therapy 3 weeks or 6 weeks
Sponsored by
Tourcoing Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteomyelitis - Foot focused on measuring Diabetes Mellitus, Antibiotic Treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient aged ≥ 18 years
  • Informed, written consent obtained from patient
  • Patient having the rights to Frenc social insurrance
  • For women of childbearing potential : any effective contraceptive is required
  • Type 1 or 2 diabetic patients
  • Diabetic patients treated non-surgically for an osteomyelitis of the forefoot affecting only one osteoarticular part/radial supported by adequate diagnostic imaging and bone biopsy performed through uninfected tissue.
  • Two peripheral pulses or transcutaneous oxygen tension measurement (TcPO2 > 30mmHg) or ankle brachial index (ABI > 0.9)
  • Patient without antibiotherapy during 2 weeks before D1.
  • Glycated hemoglobin (HbA1C) < 12% ( measured maximum 2 months before D1)
  • Use of offloading boot for diabetic foot is feasible

Exclusion Criteria:

  • Bone fragmentation, articular destruction requiring bone resection or amputation.
  • Gangrene
  • More than one osteoarticular part/radial affected
  • Contraindication for the use of offloading boot
  • Contraindication for bone biopsy
  • Contraindication for the full course of antibiotics (allergy or based on RCP)
  • Other drug-drug interaction that contraindicated the full course of antibiotics
  • Charcot foot
  • Patient undergoing radiotherapy of chimiotherapy for malignant neoplasms
  • Hepatic insufficiency (ASAT and/or ALAT > 3 times the normal level)
  • Any disease or behaviour making impossible to follow the protocol or difficult to interpret the results
  • Any disease or context making difficult to allow regular monitoring of the patient
  • Participation in other interventional research during the study
  • Curator or guardianship of patient placed under judicial protection
  • Pregnancy or lactating women

Sites / Locations

  • AP-HP Ambroise Paré
  • Centre Hospitalier de Boulogne-sur-Mer
  • Centre Hopitalier Universitaire de Brest
  • Centre Hospitalier de Béthune-Beuvry
  • Centre Hospitalier Universitaire de Caen
  • Centre Hospitalier de Compiègne-Noyon
  • Centre Hospitalier de Dunkerque
  • Centre Hospitalier de Lens
  • Centre Hospitalier Universitaire de Lille
  • GHICL Saint-Vincent de Paul
  • GHICL Saint-Philibert
  • Centre Hospitalier Universitaire de Montpellier
  • Centre Hospitalier Universitaire de Nantes
  • AP-HP Cochin
  • AP-HP Lariboisière
  • Centre Hospitalier de Roubaix
  • Centre Hospitalier Universitaire de Rouen
  • Centre Hospitalier de Valenciennes

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

3 weeks antibiotherapy

6 weeks antibiotherapy

Arm Description

Patients are treated 3 weeks with appropriate antibiotics after antibiogram evaluation.

Patients are treated 6 weeks with appropriate antibiotics after antibiogram evaluation.

Outcomes

Primary Outcome Measures

Percentage of treated patients achieving remission from the diabetic foot osteomyelitis at the end of follow-up
Remission is defined as one of following events : No relapse of infection at the initial or a contiguous site leading to make a new antibiogram. Absence of pathology exacerbation visible by radiological results (comparison with Day 0) Absence of orthopedic surgery or amputation of the foot infected initially.

Secondary Outcome Measures

Comparison in each group of patients of the time needed for a complete wound healing.
A wound healing is complete with epithelial wound closure maintained 28 days minimum of the initial site of injury caused by osteomyelitis.
Rates of reinfection at the initial site in each group of patients.
Reinfection is defined by a relapse of infection of soft tissues and osteomyelitis.
Rates of occurrence of a new wound after healing, on the same site initially traited in each group of patients.
A new wound is defined by a skin injury under the malleolus evolving over three weeks.
Rates of occurrence of a new wound after healing on the same foot but not the same infection site in each group of patients.
A new wound is defined by a skin injury under the malleolus evolving over three weeks.
Rates of occurrence of a peripheral neuroathropathy (Charcot foot) in each group of patients.
Neurologic exam includes monofilament test and tuning fork test for assessing the loss of protective sensation.
Rates of amputation in each group of patients.
Minor amputation is defined as an amputation below the ankle (malleolus). Major amputation is defined as an amputation above the ankle (malleolus).
Rates of major amputation in each group of patients.
Major amputation is defined as an amputation above the ankle (malleolus).

Full Information

First Posted
September 29, 2021
Last Updated
May 9, 2022
Sponsor
Tourcoing Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05074147
Brief Title
Comparison Between Two Durations of Antibiotherapy for Non-surgically-treated Diabetic Foot Osteomyelitis (CHRONOS-2)
Acronym
CHRONOS-2
Official Title
Three Weeks Versus Six Weeks Antibiotic Therapy for Nonsurgically Treated Diabetic Foot Osteomyelitis : a Multicenter, Randomized, Open-label and Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2022 (Anticipated)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tourcoing Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of this clinical study is to compare the efficacy and tolerance of 3 versus 6 weeks of antibiotherapy in patients with diabetic foot osteomyelitis treated medically.
Detailed Description
The fight against multi-drug resistant bacteria is a global matter and a major health public issue. The excessive exposure of microorganisms to drugs increases their ability to develop survival mechanisms, causing an emerging threat and a health challenge. Several recent studies showed that 18-35% of patients with diabetic foot infections harbored multiply drug-resistance to organisms (MDRO), the most common is Staphylococcus aureus (MRSA). Hospitalization, surgical procedures and long antibiotic therapy induce the development of MDRO or MRSA In diabetic foot, Osteomyelitis (DFO) is a well recognize risk factor for major amputation and mortality rates that occurs in more than 20% of moderate infections and 50% to 60 % of severe infections. In this context, the aim of this study is to evaluated that reducing time of antibiotic administration (3 weeks) is not substantially worse than the current treatment guidelines (6 weeks) in DFO managed nonsurgically.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteomyelitis - Foot
Keywords
Diabetes Mellitus, Antibiotic Treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
280 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
3 weeks antibiotherapy
Arm Type
Experimental
Arm Description
Patients are treated 3 weeks with appropriate antibiotics after antibiogram evaluation.
Arm Title
6 weeks antibiotherapy
Arm Type
Experimental
Arm Description
Patients are treated 6 weeks with appropriate antibiotics after antibiogram evaluation.
Intervention Type
Drug
Intervention Name(s)
Reduction in the duration of antibiotic therapy 3 weeks or 6 weeks
Intervention Description
Drugs : Rifampin (IP an PO) : 10mg/Kg/12h Ofloxacin (PO) : 200Mg/8h Levofloxacin (PO) : 500mg ot 1g/ twice a day Ciprofloxacin : IV : 400mg/8h if Pseud spp ; 400mg/12h for others Gram-negative bacilli strains; PO : 1gr/12h if Pseud spp ; 750mg/12h for others Gram-negative bacilli strains Clindamycin : 600-900mg/8h Fusidic Acid : 500mg/8h Teicoplanin : 10mg/kg/12h for 5 dosis in combination, then in monotherapy. Ceftasidim : 2g/8h if Pseud spp ; 2g/12h for others Gram-negative bacilli strains Trimethoprim-sulfamethoxazole (800mg/160mg) : once per day if patient < 80Kg ; one and a half per day if patient > 80Kg. Doxycyclin : 200mg/day Minocyclin : 100mg/8h to 12h Ceftriaxon : 1g to 2g/day in IV, IM or SC Cefotaxim : 1g to 2g/day in IV Pristinamycin : 1g thrice a day
Primary Outcome Measure Information:
Title
Percentage of treated patients achieving remission from the diabetic foot osteomyelitis at the end of follow-up
Description
Remission is defined as one of following events : No relapse of infection at the initial or a contiguous site leading to make a new antibiogram. Absence of pathology exacerbation visible by radiological results (comparison with Day 0) Absence of orthopedic surgery or amputation of the foot infected initially.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Comparison in each group of patients of the time needed for a complete wound healing.
Description
A wound healing is complete with epithelial wound closure maintained 28 days minimum of the initial site of injury caused by osteomyelitis.
Time Frame
12 months
Title
Rates of reinfection at the initial site in each group of patients.
Description
Reinfection is defined by a relapse of infection of soft tissues and osteomyelitis.
Time Frame
12 months
Title
Rates of occurrence of a new wound after healing, on the same site initially traited in each group of patients.
Description
A new wound is defined by a skin injury under the malleolus evolving over three weeks.
Time Frame
12 months
Title
Rates of occurrence of a new wound after healing on the same foot but not the same infection site in each group of patients.
Description
A new wound is defined by a skin injury under the malleolus evolving over three weeks.
Time Frame
12 months
Title
Rates of occurrence of a peripheral neuroathropathy (Charcot foot) in each group of patients.
Description
Neurologic exam includes monofilament test and tuning fork test for assessing the loss of protective sensation.
Time Frame
12 months
Title
Rates of amputation in each group of patients.
Description
Minor amputation is defined as an amputation below the ankle (malleolus). Major amputation is defined as an amputation above the ankle (malleolus).
Time Frame
12 months
Title
Rates of major amputation in each group of patients.
Description
Major amputation is defined as an amputation above the ankle (malleolus).
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient aged ≥ 18 years Informed, written consent obtained from patient Patient having the rights to Frenc social insurrance For women of childbearing potential : any effective contraceptive is required Type 1 or 2 diabetic patients Diabetic patients treated non-surgically for an osteomyelitis of the forefoot affecting only one osteoarticular part/radial supported by adequate diagnostic imaging and bone biopsy performed through uninfected tissue. Two peripheral pulses or transcutaneous oxygen tension measurement (TcPO2 > 30mmHg) or ankle brachial index (ABI > 0.9) Patient without antibiotherapy during 2 weeks before D1. Glycated hemoglobin (HbA1C) < 12% ( measured maximum 2 months before D1) Use of offloading boot for diabetic foot is feasible Exclusion Criteria: Bone fragmentation, articular destruction requiring bone resection or amputation. Gangrene More than one osteoarticular part/radial affected Contraindication for the use of offloading boot Contraindication for bone biopsy Contraindication for the full course of antibiotics (allergy or based on RCP) Other drug-drug interaction that contraindicated the full course of antibiotics Charcot foot Patient undergoing radiotherapy of chimiotherapy for malignant neoplasms Hepatic insufficiency (ASAT and/or ALAT > 3 times the normal level) Any disease or behaviour making impossible to follow the protocol or difficult to interpret the results Any disease or context making difficult to allow regular monitoring of the patient Participation in other interventional research during the study Curator or guardianship of patient placed under judicial protection Pregnancy or lactating women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eric SENNEVILLE, MD, PhD
Phone
+33 320694848
Email
esenneville@ch-tourcoing.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Solange TREHOUX, PhD
Phone
+33 320684280
Email
strehoux@ch-tourcoing.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric M SENNEVILLE, MD, PhD
Organizational Affiliation
Centre Hospitalier de Tourcoing
Official's Role
Principal Investigator
Facility Information:
Facility Name
AP-HP Ambroise Paré
City
Boulogne-Billancourt
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurélien DINH, MD
Facility Name
Centre Hospitalier de Boulogne-sur-Mer
City
Boulogne-sur-Mer
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie LEPAGE, MD
Facility Name
Centre Hopitalier Universitaire de Brest
City
Brest
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rozenn LEBERRE, MD
Facility Name
Centre Hospitalier de Béthune-Beuvry
City
Béthune
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sophie NGUYEN, MD
Facility Name
Centre Hospitalier Universitaire de Caen
City
Caen
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jocelyn MICHON, MD
Facility Name
Centre Hospitalier de Compiègne-Noyon
City
Compiègne
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amina BOURAS, MD
Facility Name
Centre Hospitalier de Dunkerque
City
Dunkerque
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline DEHECQ, MD
Facility Name
Centre Hospitalier de Lens
City
Lens
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabrice DEVEMY, MD
Facility Name
Centre Hospitalier Universitaire de Lille
City
Lille
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florence BAUDOUX, MD
Facility Name
GHICL Saint-Vincent de Paul
City
Lille
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas BACLET, MD
Facility Name
GHICL Saint-Philibert
City
Lomme
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas BACLET, MD
Facility Name
Centre Hospitalier Universitaire de Montpellier
City
Montpellier
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ariane SULTAN, MD
Facility Name
Centre Hospitalier Universitaire de Nantes
City
Nantes
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David BOUTOILLE, MD
Facility Name
AP-HP Cochin
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jocelyne M'BEMBA-ILZER, MD
Facility Name
AP-HP Lariboisière
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne-Lise MUNIER, MD
Facility Name
Centre Hospitalier de Roubaix
City
Roubaix
ZIP/Postal Code
59100
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie PICHENOT, MD
Facility Name
Centre Hospitalier Universitaire de Rouen
City
Rouen
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gaëtan PROVOST, MD
Facility Name
Centre Hospitalier de Valenciennes
City
Valenciennes
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alina TONE, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Comparison Between Two Durations of Antibiotherapy for Non-surgically-treated Diabetic Foot Osteomyelitis (CHRONOS-2)

We'll reach out to this number within 24 hrs