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Evaluation of the Efficiency of the Bone Substitute Cerament-G Locally Delivering Gentamicin in the Treatment of Chronic Osteomyelitis of Long Bones (CONVICTION)

Primary Purpose

Osteomyelitis Chronic

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Corticotomy and use of the bone substitute : Cerament-G device.
Corticotomy
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteomyelitis Chronic focused on measuring Bone infection, chronic osteomyelitis, bone substitute

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient with suspected chronic osteomyelitis (stage III of the Cierny-Mader classification) of a long bone of the tibia, femur, humerus or forearm, at the diaphysis, metaphysis or epiphysis, defined as follows:

    • Supposed inoculation > 3 months ;
    • At least one of the following clinical signs at the suspected infected site:

      • Spontaneous or supporting pain ;
      • Presence of fistula; or history of fistula discharge
      • Presence of serous or purulent flow;
      • Presence of bone exposure;
      • Local Inflammation;
      • Fever in the absence of any other explanation.
    • At least one of the following radiological signs at the suspected infected site:

      • Bone reshaping with osteolysis or periosteal apposition;
      • Presence of intramedullary abscess (if MRI performed);
      • Presence of a fistulous pathway to the intramedullary (if MRI performed);
      • Presence of bone sequestration visible on CT scan (if CT scan performed).
  • Patient in whom conventional surgical treatment of chronic osteomyelitis is possible, with decortication and corticotomy with endomedullary curettage (to eradicate bone sequestrums, reduce the inoculum, and identify the bacterium(s) involved) and secondary intramedullary residual cavity;
  • Patient in whom 3 months of systemic antibiotic therapy post-operatively are planned;
  • If osteosynthetic material is present in the infection site, this material should be considered preoperatively as completely removable during chronic osteomyelitis surgery;
  • Patient in whom a direct closure without tension is possible, or in whom a skin and soft-tissue/muscle flap can be performed within 15 days after the initial surgery;
  • Male or female patient between 18 and 80 years of age;
  • Patient who has given written informed consent to participate in the study;
  • Geographically stable patient;
  • Patient able to comply with follow-up visits, protocol schedule and therapeutic treatment, according to investigator's judgement;
  • Affiliated patient or beneficiary of a social security system

Exclusion Criteria:

  • Acute hematogenic osteomyelitis (Cierny-Mader stage I) ;
  • Cortical osteitis (Cierny-Mader stage II);
  • Septic pseudoarthrosis (Cierny-Mader stage IV);
  • Patient requiring an estimated skin and soft-tissue/muscle flap that cannot be done within 15 days after surgery for the treatment of chronic osteomyelitis;
  • Woman who is pregnant, nursing or who is considering becoming pregnant during the study period;
  • Patient participating in another interventional study that could interfere with it;
  • Patient known to have hypersensitivity to aminoglycosides (especially gentamicin), sulfites (including calcium sulfate) or calcium hydroxyapatite;
  • Contraindication to the use of Cerament-G: severe myasthenia (class IV or higher according to the MGFA classification), , severe renal insufficiency (creatinine clearance <30 mL/min according to the Cockcroft-Gault formula, or GFR < 30 ml/min/1.73² according to the CKD-EPI or MDRDs equation or, dialysis patient), pre-existing disorders of calcium metabolism (total plasma calcium (or total corrected plasma calcium according to albuminemia) outside normal laboratory values);
  • Patient with endocrine or metabolic disorders known to affect osteogenesis (e.g., Paget's disease, renal osteodystrophy, hyperthyroidism, parathyroid disorder, Ehler-Danlos syndrome, osteogenesis imperfecta);
  • Patient with one or more untreated malignant cancers (including Marjolin's ulcer), or undergoing radiotherapy or chemotherapy;
  • Adult patient protected by law, under guardianship or trusteeship.

Sites / Locations

  • CHU Amiens-Picardie
  • CHU de Besançon
  • CHU Bordeaux
  • APHP
  • CHU BrestRecruiting
  • CHU de Caen
  • CHU de Lille
  • Hospices Civils de LyonRecruiting
  • CHRU Nancy
  • CHU de NantesRecruiting
  • CHU de Nîmes
  • Hospices Civils de Lyon
  • CHU de Poitiers
  • CHU de Toulouse

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Innovative strategy

Reference strategy

Arm Description

usual medical and surgical care with corticotomy and use of a bone substitute (Cerament-G) delivering gentamicin locally (± skin and soft-tissue/muscle flap) and antibiotic therapy.

Medico-surgical usual care with corticotomy (± skin and soft-tissue/muscle flap), and antibiotic therapy.

Outcomes

Primary Outcome Measures

Incremental Cost-Utility Ratio (ICUR) between the two treatments strategies for chronic long bone osteomyelitis

Secondary Outcome Measures

Recurrence of bone infection
Proportion of patients with at least one recurrence of infection on the studied bone and time to recurrence. The Event Validation Committee will confirm the recurrence of infection.
Intraoperative and Postoperative complications
Number and types of intraoperative and postoperative complications up to 24 months (including fracture) according to CTCAE and Clavien-Dindo classifications; and proportion of patients with at least one complication during follow-up
Repeated surgeries for complication
Number of repeat surgeries for complication up to 24 months; and proportion of patients who had at least one repeat surgery for complication during follow-up
Proportion of patients with amputations
Proportion of patients with amputation of the area containing the bone studied.
Bone healing and bone remodelling/consolidation
Proportion of patients with bone healing and proportion of patients with bone remodelling/consolidation, assessed from a standard radiograph (confirmed by the Event Validation Committee).
Serious Adverse Events (SAEs) attributable to systemic antibiotic therapy.
Number and types of serious adverse events (SAEs) attributable to systemic antibiotic therapy following the first intervention; and proportion of patients with at least one SAE attributable to this systemic antibiotic therapy; within 3 months of the first intervention.
Acute renal failure
Proportion of patients with acute renal failure within 3 months of the first procedure
Adverse Events related to the use of Cerament-G
Cost of both strategies estimated at 24 months
Real cost
Real cost associated of a corticotomy procedure using Cerament-G
Estimated utility
Estimated utility measured with the EQ-5D (EuroQol Group-5 dimensions) questionnaire.
Estimated incremental cost-effectiveness ratio
Estimated incremental cost-effectiveness ratio with no recurrence of infection as efficacy endpoint
Budgetary impact analysis
Budgetary impact analysis carried out from the perspective of the French Health Insurance.

Full Information

First Posted
March 16, 2021
Last Updated
May 24, 2023
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT04805164
Brief Title
Evaluation of the Efficiency of the Bone Substitute Cerament-G Locally Delivering Gentamicin in the Treatment of Chronic Osteomyelitis of Long Bones
Acronym
CONVICTION
Official Title
Evaluation of the Efficiency of the Bone Substitute Cerament-G Locally Delivering Gentamicin in the Treatment of Chronic Osteomyelitis of Long Bones: Randomized Multicentre Study in the CRIOAc Network - CONVICTION Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 14, 2021 (Actual)
Primary Completion Date
November 14, 2026 (Anticipated)
Study Completion Date
November 14, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

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
Chronic osteomyelitis is a serious osteoarticular infection that most often occurs in the long bones (tibia, femur, humerus), responsible for significant morbidity with risk of fracture and amputation. It is due to the presence of bacteria in the bone marrow, sometimes responsible for an intraosseous abscess. Chronic osteomyelitis can have a hematogenous or more often exogenous origin, after trauma or surgery. The bacteria involved have the ability to modify their metabolism and involve persistence mechanisms (such as biofilm) making them difficult to eradicate. The treatment of chronic osteomyelitis requires surgery, i.e. corticotomy, which means opening of the bone cortex to perform an endomedullary curettage to identify the bacteria, remove any sequestration (bone fragments to which the bacteria adhere as biofilm) and reduce the bacterial inoculum. At the same time, or at a second stage, a skin and soft tissue/muscle flap may be required, especially in patients with long-standing disease with embrittlement and adhesion of the skin and soft tissue to the underlying bone. Post-operatively, the patient receives a probabilistic systemic antibiotic therapy and then a systemic antibiotic therapy targeted on the identified germ, for a period of 3 months. The effectiveness of these antibiotics is based on their ability to penetrate bone tissue. Despite the progress made in both antibiotics and surgical treatments, the probability of failure (recurrence of infection) is around 20%, and has unfortunately remained stable for more than 20 years. Cerament-G (BONESUPPORT AB Laboratory, Sweden), a synthetic bone substitute composed of hydroxyapatite, calcium sulphate, and gentamicin, fills the "dead space" formed during surgery, prevents infection of this blood-filled cavity, and promotes bone regeneration within this space (limiting the risk of fracture in the medium and long term). Cerament-G also delivers locally very high doses of gentamicin (concentration of 17.5 mg/mL in the device) for several weeks. Gentamicine is a broad-spectrum bactericidal antibiotic effective against the vast majority of bacteria involved in osteoarticular infections. It provides effective local antibiotic therapy through wide exposure and prolonged concentrations during several weeks. To date, there is no other bone substitute with antibiotics available in France. Two prospective studies have shown that Cerament-G reduces the number of infectious recurrences (about 5%). This innovation is available in France but at a high price (between 2,500 and 4,000 euros) and is not currently reimbursed. However, the use of this product would make it possible to improve the health and quality of life of patients while avoiding certain consumption of resources.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteomyelitis Chronic
Keywords
Bone infection, chronic osteomyelitis, bone substitute

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Innovative strategy
Arm Type
Experimental
Arm Description
usual medical and surgical care with corticotomy and use of a bone substitute (Cerament-G) delivering gentamicin locally (± skin and soft-tissue/muscle flap) and antibiotic therapy.
Arm Title
Reference strategy
Arm Type
Active Comparator
Arm Description
Medico-surgical usual care with corticotomy (± skin and soft-tissue/muscle flap), and antibiotic therapy.
Intervention Type
Procedure
Intervention Name(s)
Corticotomy and use of the bone substitute : Cerament-G device.
Intervention Description
Corticotomy and Cerament-G device
Intervention Type
Procedure
Intervention Name(s)
Corticotomy
Intervention Description
Corticotomy
Primary Outcome Measure Information:
Title
Incremental Cost-Utility Ratio (ICUR) between the two treatments strategies for chronic long bone osteomyelitis
Time Frame
At 24 months (M24)
Secondary Outcome Measure Information:
Title
Recurrence of bone infection
Description
Proportion of patients with at least one recurrence of infection on the studied bone and time to recurrence. The Event Validation Committee will confirm the recurrence of infection.
Time Frame
At 24 months (M24)
Title
Intraoperative and Postoperative complications
Description
Number and types of intraoperative and postoperative complications up to 24 months (including fracture) according to CTCAE and Clavien-Dindo classifications; and proportion of patients with at least one complication during follow-up
Time Frame
From inclusion to 24 months (M24)
Title
Repeated surgeries for complication
Description
Number of repeat surgeries for complication up to 24 months; and proportion of patients who had at least one repeat surgery for complication during follow-up
Time Frame
From first surgery to 24 months (M24)
Title
Proportion of patients with amputations
Description
Proportion of patients with amputation of the area containing the bone studied.
Time Frame
At 24 months (M24)
Title
Bone healing and bone remodelling/consolidation
Description
Proportion of patients with bone healing and proportion of patients with bone remodelling/consolidation, assessed from a standard radiograph (confirmed by the Event Validation Committee).
Time Frame
At 12 months (M12)
Title
Serious Adverse Events (SAEs) attributable to systemic antibiotic therapy.
Description
Number and types of serious adverse events (SAEs) attributable to systemic antibiotic therapy following the first intervention; and proportion of patients with at least one SAE attributable to this systemic antibiotic therapy; within 3 months of the first intervention.
Time Frame
Within 3 months of the first intervention (M3)
Title
Acute renal failure
Description
Proportion of patients with acute renal failure within 3 months of the first procedure
Time Frame
Within 3 months of the first procedure (M3)
Title
Adverse Events related to the use of Cerament-G
Description
Cost of both strategies estimated at 24 months
Time Frame
At 24 months (M24)
Title
Real cost
Description
Real cost associated of a corticotomy procedure using Cerament-G
Time Frame
24 months (M24)
Title
Estimated utility
Description
Estimated utility measured with the EQ-5D (EuroQol Group-5 dimensions) questionnaire.
Time Frame
At inclusion, at Week 4/Week 6, Month 3, Month 6, Month12, Month 18 and Month 24 (usual follow-up visits) as well as after each repeat surgery according to the same schedule
Title
Estimated incremental cost-effectiveness ratio
Description
Estimated incremental cost-effectiveness ratio with no recurrence of infection as efficacy endpoint
Time Frame
At 24 months (M24)
Title
Budgetary impact analysis
Description
Budgetary impact analysis carried out from the perspective of the French Health Insurance.
Time Frame
24 months (M24)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient with suspected chronic osteomyelitis (stage III of the Cierny-Mader classification) of a long bone of the tibia, femur, humerus or forearm, at the diaphysis, metaphysis or epiphysis, defined as follows: Supposed inoculation > 3 months ; At least one of the following clinical signs at the suspected infected site: Spontaneous or supporting pain ; Presence of fistula; or history of fistula discharge Presence of serous or purulent flow; Presence of bone exposure; Local Inflammation; Fever in the absence of any other explanation. At least one of the following radiological signs at the suspected infected site: Bone reshaping with osteolysis or periosteal apposition; Presence of intramedullary abscess (if MRI performed); Presence of a fistulous pathway to the intramedullary (if MRI performed); Presence of bone sequestration visible on CT scan (if CT scan performed). Patient in whom conventional surgical treatment of chronic osteomyelitis is possible, with decortication and corticotomy with endomedullary curettage (to eradicate bone sequestrums, reduce the inoculum, and identify the bacterium(s) involved) and secondary intramedullary residual cavity; Patient in whom 3 months of systemic antibiotic therapy post-operatively are planned; If osteosynthetic material is present in the infection site, this material should be considered preoperatively as completely removable during chronic osteomyelitis surgery; Patient in whom a direct closure without tension is possible, or in whom a skin and soft-tissue/muscle flap can be performed within 15 days after the initial surgery; Male or female patient between 18 and 80 years of age; Patient who has given written informed consent to participate in the study; Geographically stable patient; Patient able to comply with follow-up visits, protocol schedule and therapeutic treatment, according to investigator's judgement; Affiliated patient or beneficiary of a social security system Exclusion Criteria: Acute hematogenic osteomyelitis (Cierny-Mader stage I) ; Cortical osteitis (Cierny-Mader stage II); Septic pseudoarthrosis (Cierny-Mader stage IV); Patient requiring an estimated skin and soft-tissue/muscle flap that cannot be done within 15 days after surgery for the treatment of chronic osteomyelitis; Woman who is pregnant, nursing or who is considering becoming pregnant during the study period; Patient participating in another interventional study that could interfere with it; Patient known to have hypersensitivity to aminoglycosides (especially gentamicin), sulfites (including calcium sulfate) or calcium hydroxyapatite; Contraindication to the use of Cerament-G: severe myasthenia (class IV or higher according to the MGFA classification), , severe renal insufficiency (creatinine clearance <30 mL/min according to the Cockcroft-Gault formula, or GFR < 30 ml/min/1.73² according to the CKD-EPI or MDRDs equation or, dialysis patient), pre-existing disorders of calcium metabolism (total plasma calcium (or total corrected plasma calcium according to albuminemia) outside normal laboratory values); Patient with endocrine or metabolic disorders known to affect osteogenesis (e.g., Paget's disease, renal osteodystrophy, hyperthyroidism, parathyroid disorder, Ehler-Danlos syndrome, osteogenesis imperfecta); Patient with one or more untreated malignant cancers (including Marjolin's ulcer), or undergoing radiotherapy or chemotherapy; Adult patient protected by law, under guardianship or trusteeship.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tristan FERRY
Phone
+33 4 72 07 24 81
Email
tristan.ferry@chu-lyon.fr
Facility Information:
Facility Name
CHU Amiens-Picardie
City
Amiens
ZIP/Postal Code
80054
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benoit BRUNSCHWEILER
First Name & Middle Initial & Last Name & Degree
Benoit BRUNSCHWEILER, MD
First Name & Middle Initial & Last Name & Degree
Cédric JOSEPH, MD
Facility Name
CHU de Besançon
City
Besançon
ZIP/Postal Code
25030
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pauline SERGENT
First Name & Middle Initial & Last Name & Degree
Pauline SERGENT, MD
First Name & Middle Initial & Last Name & Degree
Kévin BOUILLER, MD
First Name & Middle Initial & Last Name & Degree
Isabelle PLUVY, MD
Facility Name
CHU Bordeaux
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric-Antoine DAUCHY
First Name & Middle Initial & Last Name & Degree
Frédéric-Antoine DAUCHY, MD
First Name & Middle Initial & Last Name & Degree
Thierry FABRE, MD
Facility Name
APHP
City
Boulogne Billancourt
ZIP/Postal Code
92104
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas BAUER
First Name & Middle Initial & Last Name & Degree
Thomas BAUER, MD
First Name & Middle Initial & Last Name & Degree
Aurélien DINH, MD
Facility Name
CHU Brest
City
Brest
ZIP/Postal Code
29200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas WILLIAMS
First Name & Middle Initial & Last Name & Degree
Thomas WILLIAMS, MD
First Name & Middle Initial & Last Name & Degree
Séverine ANSART, MD
Facility Name
CHU de Caen
City
Caen
ZIP/Postal Code
14033
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Goulven ROCHCONGAR
First Name & Middle Initial & Last Name & Degree
Goulven ROCHCONGAR, MD
First Name & Middle Initial & Last Name & Degree
Jocelyn MICHON, MD
Facility Name
CHU de Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric SENNEVILLE
First Name & Middle Initial & Last Name & Degree
Eric SENNEVILLE, MD
First Name & Middle Initial & Last Name & Degree
Henry MIGAUD, MD
First Name & Middle Initial & Last Name & Degree
Louise PASQUESOONE, MD
Facility Name
Hospices Civils de Lyon
City
Lyon
ZIP/Postal Code
69004
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tristan FERRY
First Name & Middle Initial & Last Name & Degree
Tristan FERRY, MD
First Name & Middle Initial & Last Name & Degree
cécile BATAILLER, MD
First Name & Middle Initial & Last Name & Degree
Elliot SAPPEY-MARINIER, MD
First Name & Middle Initial & Last Name & Degree
Sophie BROSSET, MD
First Name & Middle Initial & Last Name & Degree
Mathilde LHERM, MD
Facility Name
CHRU Nancy
City
Nancy
ZIP/Postal Code
54000
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Didier MAINARD
First Name & Middle Initial & Last Name & Degree
Didier MAINARD, MD
First Name & Middle Initial & Last Name & Degree
Sibylle BEVILACQUA, MD
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christophe Nich
First Name & Middle Initial & Last Name & Degree
Christophe Nich, MD
First Name & Middle Initial & Last Name & Degree
David BOUTOILLE, MD
Facility Name
CHU de Nîmes
City
Nîmes
ZIP/Postal Code
30029
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas CELLIER
First Name & Middle Initial & Last Name & Degree
Nicolas CELLIER, MD
First Name & Middle Initial & Last Name & Degree
Paul LOUBET, MD
Facility Name
Hospices Civils de Lyon
City
Pierre-Bénite
ZIP/Postal Code
69310
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michel-Henry FESSY
First Name & Middle Initial & Last Name & Degree
Michel-Henry FESSY, MD
First Name & Middle Initial & Last Name & Degree
Claire TRIFFAULT-FILLIT, MD
First Name & Middle Initial & Last Name & Degree
Nicolas SIGAUX, MD
First Name & Middle Initial & Last Name & Degree
Antoine PIERREFEU, MD
Facility Name
CHU de Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre PRIES
First Name & Middle Initial & Last Name & Degree
Pierre PRIES, MD
First Name & Middle Initial & Last Name & Degree
Gwenaël LE MOAL, MD
Facility Name
CHU de Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre DELOBEL
First Name & Middle Initial & Last Name & Degree
Pierre DELOBEL, MD
First Name & Middle Initial & Last Name & Degree
Nicolas REINA, MD

12. IPD Sharing Statement

Learn more about this trial

Evaluation of the Efficiency of the Bone Substitute Cerament-G Locally Delivering Gentamicin in the Treatment of Chronic Osteomyelitis of Long Bones

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