A Phase 4 interventional study of Ceftriaxone and Usual Antibiotics (Cloxacillin, Cefazolin, Daptomycin) in Staphylococcal Infections, Osteomyelitis and CNS Infection, sponsored by Vancouver Island Health Authority. Status unknown at 2 sites in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-28.
Sponsored by Vancouver Island Health Authority · Phase 4, Interventional, and Treatment
Patients who are admitted to hospital with serious infections, such as those in bone, joints or spine, require a long course of intravenous (IV) antibiotics. After an initial treatment course in hospital or through a dedicated outpatient antibiotic program many patients can complete their treatment course at home. Such infections are often caused by bacteria called Staphylococci, and currently there are three antibiotic options used routinely. A fourth antibiotic, ceftriaxone, is a promising alternative; it is also effective against Staphylococci, and is more convenient, less costly and easier to give at home, however, it has not been studied thoroughly in a prospective manner. This study will compare ceftriaxone to routinely used antibiotics (cloxacillin, cefazolin or daptomycin) to see if ceftriaxone is equally as safe and efficacious in curing deep-seated Staphylococcal infections in patients receiving home IV antibiotics. Patients with deep-seated infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) or coagulase-negative Staphylococcal species will be randomly assigned home IV treatment with ceftriaxone OR one of the three other antibiotics before leaving the hospital. Patients will then receive usual care from an Infectious Disease physician and Home IV team. The study team will assess whether cure has been achieved by the end of the IV treatment, follow-up at 6 months to see if patients remain infection-free, and record any side-effects of treatment. The overall goal is to determine whether ceftriaxone can be considered non-inferior to usual antibiotic treatment in treating Staphylococcal infections in a home IV setting.
The use of ceftriaxone for deep-seated Staphylococcal infections requiring prolonged IV treatment is a practice that has already evolved both locally and globally despite the absence of high-quality clinical data. Retrospective studies that support the use of ceftriaxone for this indication, including those that currently inform Infectious Diseases Society of America (IDSA) guidelines, unanimously agree that prospective, randomized data is urgently needed. Our study is the next natural step in the research process and would greatly add to the body of evidence informing this practice by addressing current knowledge gaps. On a clinical level, demonstrating non-inferiority of ceftriaxone would allow its use in a population of patients currently ineligible for outpatient antibiotic treatment or in cases where broader, more expensive agents are currently employed. This would facilitate more rapid discharge from hospital, lead to substantial cost savings, and have a considerable impact on antimicrobial stewardship. Most importantly, it would improve the quality of life of patients by allowing them to be treated at home in cases when multi-dose home IV administration is a barrier to discharge. This study would address the need to support and harmonize current practice at Island Health, increase the level of evidence in current guidelines and improve patient care both locally and globally.
This is a prospective, randomized, controlled, unblinded trial with a pragmatic design. The goal is to assess whether the intervention is non-inferior to standard therapies in achieving the primary outcome. Patients will be drawn from inpatient populations and patients treated through an outpatient antibiotic therapy clinic who are eligible for further IV treatment through a home intravenous therapy program. Patients meeting inclusion criteria as described will be asked to participate and informed consent obtained. Once informed consent is obtained patients will be randomized to receive ceftriaxone or standard therapies (cloxacillin, cefazolin, daptomycin) as determined by the treating infectious diseases physician. Patients will have deep-seated infections such as:
Infections will be confirmed to have been caused by methicillin-sensitive Staphylococcus aureus or a coagulase-negative Staphylococcal species through microbiological testing. Susceptibility testing will ensure that the isolate is susceptible to the study drug and at least one of the standard therapies.
Once the patient is randomized all other aspects of care will follow usual home IV therapy policies and procedures. Neither the patient nor the clinical team will be blinded to the study drug the patient is receiving. Duration of treatment will be decided by the treating infectious diseases clinician based on infection site and available guidelines. Baseline data will be collected by the study team at the time of randomization.
The patient will be followed up in the usual manner by their infectious diseases physician. Data will be collected in a standardized manner at the pre-specified end of antibiotic therapy. Clinical cure (primary outcome) will be determined based on this data.
Adverse event rates will be collected throughout the study period. At six months post-randomization the study team will assess for any markers of treatment failure (see secondary outcomes).
Plan for statistical analysis is pre-specified in the protocol and will be completed with the assistance of biostatistics staff at the University of Victoria. Specific information on the protection of patient confidentiality and data integrity is outlined in the study protocol. Ethics approval has been granted by the Clinical Research Ethics Board at Vancouver Island Health Authority.
6,687 studies on the registry are indexed under Infections; 807 are open to participants now.
This study's planned enrollment of 310 is above the median of 120 across 4,200 interventional studies indexed under Infections.
Browse Infections studies →Vancouver Island Health Authority is the lead sponsor of 10 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
were referred to and assessed by an Infectious Disease physician in the form of a clinical consult as either:
Exclusion Criteria:
Ceftriaxone 2g IV q24hvia Gravity (or q12h in the case of CNS infections) Duration dependent on site of infection, determined by treating infectious diseases (ID) clinicians based on accepted clinical guidelines.
Drug: Ceftriaxone
"Usual Antibiotics" to treat methicillin-susceptible Staphylococcal infections * Cloxacillin 2g IV q4h via Pump (dose adjusted for renal function) * Cefazolin 2g IV q8h via Preloaded Syringe (dose adjusted for renal function) * Daptomycin 6-10mg/kg IV daily via Gravity (dose will be determined based on the severity of infection as per discretion of the ID clinician and in accordance with most recent evidence) * Duration dependent on site of infection, determined by treating infectious diseases clinicians based on accepted clinical guidelines.
Drug: Usual Antibiotics (Cloxacillin, Cefazolin, Daptomycin)
Participants with methicillin-sensitive deep-seated staphylococcal infections eligible for treatment on home IV will be randomly assigned to a "treatment" group of ceftriaxone or "standard therapy/usual antibiotics" with either cloxacillin, cefazolin or daptomycin. The treatment with one of the three "standard therapies/usual antibiotics" will be left to the discretion of the treating Infectious Disease doctor, in line with current standards of practice.
Also known as: Rocephin
Participants with methicillin-sensitive deep-seated staphylococcal infections eligible for treatment on home IV will be randomly assigned to a "treatment" group of ceftriaxone or "standard therapy/usual antibiotics" with either cloxacillin, cefazolin or daptomycin. The treatment with one of the three "standard therapies/usual antibiotics" will be left to the discretion of the treating Infectious Disease doctor, in line with current standards of practice.
Also known as: Cloxacillin, Cefazolin, Daptomycin, Ancef, Cubicin
Clinical cure rate of deep-seated methicillin sensitive Staphylococcal infections
Clinical cure of deep-seated MSSA and CoNS infections will be defined by improvement in clinical parameters, imaging findings and laboratory values at the time of completion of a pre-specified duration of antibiotic treatment based on infection site and clinical guidelines. Clinical cure defined by treating infectious diseases clinicians based on composite of: * Resolution of signs and symptoms of deep-seated infection * Improvement in inflammatory markers; defined as a C-reactive protein (CRP) less than 50% of initial CRP value * Improvement in follow- up imaging when conducted, as determined by the interpreting radiologist
Time frame: Up to 6 months post-randomization
Treatment failure at six months post-randomization
Failure of treatment at six months post-randomization will be defined by: * Readmission to hospital for complications or progression of the specific infection being treated * Need for further surgical source control procedures * Additional antibiotics required for recurrent infection by the same organism, in the same location after initial treatment course was completed This will be determined by chart review completed by study team members.
Time frame: At six months following randomization
Adverse event rate
All adverse events related to study drug with specific safety data on rates of anaphylaxis, Clostridium difficile infections, dermatologic eruptions, hepatic enzyme abnormalities, leukopenia, thrombocytopenia, gastrointestinal upset and acute kidney injury between the two treatment arms.
Time frame: Up to 6 months post-randomization
Rate of antibiotic substitution or discontinuation
If antibiotic needs to be substituted or discontinued for any reason
Time frame: Up to 6 months post-randomization
Duration of therapy
Duration of therapy as compared by infection type across both arms
Time frame: Up to 6 months post-randomization
Plan to share: Yes — De-identified participant data for all primary and secondary outcome measures will be made available within 6 months of study completion.
Supporting information: Study protocol, Sap, Icf
This study is status unknown, as verified in Oct 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Vancouver Island Health Authority