Febrile Neutropenia
Conditions
Brief summary
The purpose of this study is to evaluate the benefits and side effects of daptomycin compared to placebo for the treatment of neutropenic fever.
Detailed description
To determine whether the percentage of neutropenic subjects that become afebrile by five days after fever first develops is higher when daptomycin compared to placebo is added at the same time as anti gram-negative therapy. The five day time point is selected because it is at this point where it is recommended to add antifungal therapy to the treatment regimen if the patient is still febrile.
Interventions
DRUGDaptomycin
8 MG/KG IV
OTHERSaline Placebo
50 ml normal saline once daily
Sponsors
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients in the above categories who are currently undergoing chemotherapy. 2. Patients at least 18 of age. 3. Patient expected to reach an absolute granulocyte count of \<100 cells/mm3 4. Patients who have given written consent because of the above criteria must have at least one temperature of greater or equal to 38.3° or temperatures \> 38o on at least two occasions before study drug is administered.
Exclusion criteria
1. Patients with lymphoma or with solid tumor undergoing initial chemotherapy. Their neutropenia is of insufficient duration for adequate test of the value of an anti-gram positive antibiotic. 2. Patients undergoing auto-transplantation, for the same reason as above. 3. Patients with evidence of a clinical infection such as presence of a pulmonary infiltrate by x-ray or clinical evidence for the presence of cellulitis. 4. Patients who have received daptomycin in the two weeks prior to enrollment. 5. Patients with concomitant use of vancomycin. 6. Patients with creatinine clearance \< 30 ml/min or CPK \> 3x normal 7. Patients with significant hepatic dysfunction, defined as baseline liver function tests \> 5x above normal. 8. Patients with known allergy to daptomycin. 9. Patients previously in this study. 10. Women of child bearing age who are either lactating or pregnant (as evidenced by a positive urine pregnancy test or positive serum beta-HCG). 11. Patients previously enrolled in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Afebrile Neutropenic Subjects | 5 days | To determine whether the percentage of neutropenic subjects that become afebrile by five days after fever first develops. |
Countries
United States
Participant flow
Recruitment details
First subject was enrolled on 14April2011 and last subject enrolled was 01November2012. All subjects were enrolled as inpatients at University of Rochester Medical Center.
Pre-assignment details
All subjects, once consent was obtained were considered enrolled. If they developed a fever they were then randomized to study drug or placebo. If they did not develop neutropenic fever they did not receive study drug or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Daptomycin Daptomycin intravenous 8mg/kg once per day 5-10 days.
Daptomycin : 8 mg/kg once daily
Daptomycin : 8 MG/KG IV | 18 |
| Saline Placebo Saline solution
Saline Placebo : 50 ml normal saline once daily
Daptomycin : 8 mg/kg once daily | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | Daptomycin | Saline Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 17 Participants | 31 Participants |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 23 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 18 | 5 / 18 |
| serious Total, serious adverse events | 3 / 18 | 2 / 18 |
Outcome results
Primary
Percentage of Afebrile Neutropenic Subjects
To determine whether the percentage of neutropenic subjects that become afebrile by five days after fever first develops.
Time frame: 5 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daptomycin | Percentage of Afebrile Neutropenic Subjects | 1 participants |
| Saline Placebo | Percentage of Afebrile Neutropenic Subjects | 1 participants |