None listed
Conditions
Brief summary
A large proportion of health care facilities in developing countries does not have the diagnostic armamentarium necessary to undertake a complete preemptive therapy for high-risk patients with persistent neutropenic fever. Likewise, the use of liposomal amphotericin B is limited by its cost. Therefore, we designed this study to determine the optimal time for starting empirical antifungal therapy with amphotericin B deoxycholate in high-risk patients with persistent neutropenic fever, which could provide a timely resolution of symptoms and potentially a reduction in mortality. This is a single-center, randomized, double-masked, placebo-controlled, parallel-group study. Eligible patients will be randomized on the fourth day of fever to treatment A (early therapy) or B (delayed therapy). In treatment A, amphotericin B deoxycholate will be initiated on the fourth day of fever. In treatment B, placebo will be initiated on the fourth day of fever and, on the sixth day, the latter will be switched to amphotericin B deoxycholate. The primary outcome will be the time to fever resolution after the start of amphotericin B deoxycholate.
Interventions
Initiation of amphotericin B deoxycholate on day 4 (early initiation or treatment A) .
Fourth day of fever (38.3 degrees Celsius or more), i.e., persistent fever (i.e., despite being treated with broad-spectrum antibiotics).
Administration method: First, these patients will receive 1 L of normal saline (NaCl 0.9%) intravenously for 1 hour. Then, they will receive 1 L of 5% dextrose in water (D5W) plus 1 mg/kg daily of amphotericin B deoxycholate plus one vial (10 mL) of Multiple Vitamins for I
Initiation of amphotericin B deoxycholate on day 4 (early initiation or treatment A) . Fourth day of fever (38.3 degrees Celsius or more), i.e., persistent fever (i.e., despite being treated with broad-spectrum antibiotics). Administration method: First, these patients will receive 1 L of normal saline (NaCl 0.9%) intravenously for 1 hour. Then, they will receive 1 L of 5% dextrose in water (D5W) plus 1 mg/kg daily of amphotericin B deoxycholate plus one vial (10 mL) of Multiple Vitamins for Infusion (Dextrevit Registered Trademark) given by slow infusion (12 hours). The 12-hour infusion is a combination of the D5W, amphotericin B deoxycholate and Multiple Vitamins, which are all given once daily. Amphotericin B deoxycholate will continue for at least 48 hours after the patient is afebrile and his absolute neutrophil count is 500 cells/mm3 or more. The latter decision will be made by the research team. A team member will also monitor adherence on a daily basis.
Sponsors
Adrian Camacho-Ortiz
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Neutropenic fever, 2. High-risk patient, 3. Persistent fever, 4. No source of infection at the time of randomization.
Exclusion criteria
1. Hemodynamic instability before randomization, 2. Chronic kidney disease stage 4 and 5. 3. Use of amphotericin B deoxycholate in the last four weeks, 4. Respiratory failure (PaO 2 / FiO 2 <301) prior to randomization, 5. History of severe adverse reaction to amphotericin B deoxycholate, 6. Pregnancy, 7. History of invasive fungal disease, 8. Chronic liver disease.
Outcome results
None listed