DALICATH: Dalbavancin Versus Standard Antibiotic Therapy for Catheter-related Bloodstream Infections Due to Staphylococcus Aureus

Sponsor

Centre Hospitalier Annecy Genevois (Other)

Overall Status

Withdrawn

CT.gov ID

NCT05117398

Collaborator

Centre Hospitalier de Perigueux (Other), Advanz Pharma (Industry), French National Network of Clinical Research in Infectious Diseases (RENARCI) (Other), Centre National de Reférence des Staphylocoques (Other), Nantes University Hospital (Other), APHP (Other)

Enrollment

Arms

34.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The DALICATH study aim to demonstrate the non-inferiority of a single administration of 1500 mg of dalbavancin compared with standard documented antibiotic therapy for 14 days according to national guidelines.

Condition or Disease	Intervention/Treatment	Phase
Catheter Bacteremia Staphylococcus Aureus Infection	Drug: Dalbavancin Other: Standard of care	Phase 3

Detailed Description

Catheter-related bloodstream infections (CR-BSIs) are the most common nosocomial bloodstream infections, with an incidence as high as 8.5 to 19.8 infections per 1000 catheter-days. Staphylococcus aureus is involved in about 20% of CR-BSIs and associated with significant morbidity, mortality (9.3%), prolonged hospital stay (+ 9 days), and healthcare costs (35 000 € to 65 000 € per case). S. aureus CR-BSIs occurs mainly in frail patients with a port of catheter for chemotherapy or parenteral nutrition.

According to international guidelines, management of CR-BSIs due to S. aureus includes the removal and replacement of the infected catheter and a 14-day intravenous (IV) antibiotic therapy. Therefore, the management of CR-BSIs due to S. aureus requires the insertion of a new intravenous catheter. In turn, the new catheter can also lead to new septic complications and limit the patients' autonomy. Non-adherence to these recommendations leads to over-mortality and costs. To date, it is not recommended to switch to oral antibiotics in such infections.

Dalbavancin is a new glycopeptide antibiotic, with an excellent bactericidal activity against Gram-positive bacteria, especially S. aureus, and a prolonged half-life of 14 to 15 days. As a comparison, half-life of antibiotics usually used for CR-BSIs due to S. aureus, i.e. penicillin or glycopeptide, as-per sensitivity to methicillin is much lower: 1.5 to 9 hours. Such prolonged half-life allows one IV injection to be sufficient and effective over 14 days of treatment. This remarkable characteristic should allow patients to be promptly discharged from hospital without monitoring.

The hypothesis is that in patients with CR-BSIs due to S. aureus, after catheter removal, dalbavancin could be administered intravenously in a single administration after catheter removal and be as effective as standard documented antibiotic therapy for 14 days according to national guidelines.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Phase III, pragmatic, open-label, non-inferiority, randomized (1:1), multicenter trial, in patients with non-complicated CR-BSI due to S. aureus, with two parallel groups receiving 14 days of active antimicrobial therapy.Phase III, pragmatic, open-label, non-inferiority, randomized (1:1), multicenter trial, in patients with non-complicated CR-BSI due to S. aureus, with two parallel groups receiving 14 days of active antimicrobial therapy.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Open-label Controlled Trial Evaluating a Single-dose Intravenous Dalbavancin Versus Standard Antibiotic Therapy During Catheter-related Bloodstream Infections Due to Staphylococcus Aureus

Anticipated Study Start Date :

Jan 3, 2022

Anticipated Primary Completion Date :

Apr 4, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dalbavancin Dalbavancin (Xydalba®) 1500 mg - One unique dose	Drug: Dalbavancin A single-dose of IV dalbavancin 1500 mg
Experimental: Standard documented antibiotic therapy for 14 days according to national guidelines. As currently recommended, investigators will be encouraged to use the intravenous route for the entire duration of treatment. However, in order to interfere as little as possible with usual practice in each center, the antimicrobial therapy will be let to the choice of the physician in charge of the patient after a minimum of 7 days of intravenous treatment.	Other: Standard of care Standard Antibiotic therapy according national recommendations

Arm

Intervention/Treatment

Experimental: Dalbavancin

Dalbavancin (Xydalba®) 1500 mg - One unique dose

Drug: Dalbavancin

A single-dose of IV dalbavancin 1500 mg

Experimental: Standard documented antibiotic therapy for 14 days according to national guidelines.

As currently recommended, investigators will be encouraged to use the intravenous route for the entire duration of treatment. However, in order to interfere as little as possible with usual practice in each center, the antimicrobial therapy will be let to the choice of the physician in charge of the patient after a minimum of 7 days of intravenous treatment.

Other: Standard of care

Standard Antibiotic therapy according national recommendations

Outcome Measures

Primary Outcome Measures

Cure rate [DAY 30]
Clinical cure without relapse

Secondary Outcome Measures

Cure rate [DAY 14;DAY 90]
Clinical cure
Mortality rate [DAY 90]
Death all-cause
Bloodstream clearance [DAY 14]
Time from first positive blood culture to first negative blood cultures
Patient's quality of life [BASELINE; DAY 14; DAY 30; DAY 90]
Autonomy, pain and anxiety using 5-level EQ-5D scale
Hospitalization length of stay [DAY 90]
Hospitalization duration in days
Cost-utility analyses [DAY 90]
Cost per avoided relapse
Occurrence of any adverse event (AE and SAE) [DAY 90]
Proportion of patients with any adverse event

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged at least 18 years;
Blood cultures positive for S. aureus, obtained within 72 hours before randomization (the date considered is the date of the sampling, not the results);
CR-BSI, defined as:

One positive blood culture AND Local signs of infection at the catheter site OR at least one positive blood culture obtained from the catheter and the peripheral vein, AND A differential period between catheter versus peripheral blood culture positivity of at least 2h as recommended AND Same S. aureus isolate (same phenotype) identified from the catheter and the peripheral vein blood cultures;

Intravascular catheter - implantable venous access device - removed before randomization;
Informed consent form date and signed by the patient.

Exclusion Criteria:

Polymicrobial infection
More than 72 hours of active antibiotic treatment targeting S. aureus (in-vitro susceptibility) administered prior to randomization;
Patient with known valvulopathy, previous history of endocarditis, or suspicion of infective endocarditis by physician in charge;
Suspicion of any other deep focus infections, such as arthritis, pneumonia, osteomyelitis, or meningitis, presence of cerebral or peripheral emboli (arterial occlusion);
Thrombophlebitis
Failure to remove any intravascular catheter which was present when first positive blood culture
Signs of infection associated with quick SOFA score ≥ 2 at randomization
Patients with foreign bodies such as: prosthetic heart valve, endovascular prosthesis, ventriculo-atrial shunt, pacemaker, or an automated implantable cardioverter defibrillator (AICD) device
Severe liver disease (Child-Pugh C)
Severely immunocompromised patients:
Neutropenia (< 500 neutrophils/µL) at randomization;
Hematopoietic stem cell transplantation within the past 6 months or planned during treatment period;
Solid organ transplant;
Contraindication to dalbavancin and/or glycopeptide
Life expectancy < 3 months
Injection drug user
Pregnant or breastfeeding women
For premenopausal women: failure to use highly-effective contraceptive methods for 1 month after receiving study drug
Participation in other interventional trials within the previous three months or ongoing;
Persons held in an institution by legal or official order;
Patients under guardianship or curators;
Patients unable to give a free and informed consent;
Patient not affiliated to a social security scheme: obligation of affiliation to a social security scheme or to be a beneficiary.