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

Three Weeks Versus Six Weeks Antibiotic Therapy for Nonsurgically Treated Diabetic Foot Osteomyelitis : a Multicenter, Randomized, Open-label and Controlled Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteomyelitis - Foot
• Intervention / Treatment: Drug: Reduction in the duration of antibiotic therapy 3 weeks or 6 weeks

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.

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Eric SENNEVILLE, MD, PhD; Phone Number: +33 320694848; Email: esenneville@ch-tourcoing.fr
• Study Contact Backup: Name: Solange TREHOUX, PhD; Phone Number: +33 320684280; Email: strehoux@ch-tourcoing.fr

Study Locations

• France
  • Boulogne-Billancourt, France
    • AP-HP Ambroise Pare
    • Contact: Aurélien DINH, MD
  • Boulogne-sur-Mer, France
    • Centre Hospitalier de Boulogne-sur-mer
  • Brest, France
    • Centre Hopitalier Universitaire de Brest
    • Contact: Rozenn LEBERRE, MD
  • Béthune, France
    • Centre Hospitalier de Béthune-Beuvry
    • Contact: Sophie NGUYEN, MD
  • Caen, France
    • Centre Hospitalier Universitaire de Caen
    • Contact: Jocelyn MICHON, MD
  • Compiègne, France
    • Centre Hospitalier de Compiègne-Noyon
    • Contact: Amina BOURAS, MD
  • Dunkerque, France
    • Centre Hospitalier de Dunkerque
    • Contact: Caroline DEHECQ, MD
  • Lens, France
    • Centre Hospitalier de LENS
    • Contact: Fabrice DEVEMY, MD
  • Lille, France
    • Centre Hospitalier Universitaire de Lille
    • Contact: Florence BAUDOUX, MD
  • Lille, France
    • GHICL Saint-Vincent de Paul
    • Contact: Nicolas BACLET, MD
  • Lomme, France
    • GHICL Saint-Philibert
    • Contact: Nicolas BACLET, MD
  • Montpellier, France
    • Centre Hospitalier Universitaire de Montpellier
    • Contact: Ariane SULTAN, MD
  • Nantes, France
    • Centre Hospitalier Universitaire de Nantes
    • Contact: David BOUTOILLE, MD
  • Paris, France
    • AP-HP Cochin
    • Contact: Jocelyne M'BEMBA-ILZER, MD
  • Paris, France
    • AP-HP Lariboisiere
    • Contact: Anne-Lise MUNIER, MD
  • Roubaix, France, 59100
    • Centre Hospitalier de Roubaix
    • Contact: Marie PICHENOT, MD
  • Rouen, France
    • Centre Hospitalier Universitaire de Rouen
    • Contact: Gaëtan PROVOST, MD
  • Valenciennes, France
    • Centre Hospitalier de Valenciennes
    • Contact: Alina TONE, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 3 weeks antibiotherapy; Patients are treated 3 weeks with appropriate antibiotics after antibiogram evaluation.	Drug: Reduction in the duration of antibiotic therapy 3 weeks or 6 weeks; 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
EXPERIMENTAL: 6 weeks antibiotherapy; Patients are treated 6 weeks with appropriate antibiotics after antibiogram evaluation.	Drug: Reduction in the duration of antibiotic therapy 3 weeks or 6 weeks; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months
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.	12 months
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.	12 months
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.	12 months
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.	12 months
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).	12 months
Rates of major amputation in each group of patients.	Major amputation is defined as an amputation above the ankle (malleolus).	12 months

Collaborators and Investigators

• Sponsor: Tourcoing Hospital
• Investigators: Principal Investigator: Eric M SENNEVILLE, MD, PhD, Centre Hospitalier de Tourcoing

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2022
• Primary Completion (ANTICIPATED): November 1, 2024
• Study Completion (ANTICIPATED): November 1, 2026

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (ACTUAL): October 12, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 16, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Antibiotic Treatment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Infections; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Infectious; Foot Ulcer; Diabetic Foot; Osteomyelitis; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: RIPH_2019_04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No