Staphylococcal Skin Infections
Conditions
Keywords
Complicated Skin and Skin-Structure Infections, Daptomycin, MRSA, Diabetic Foot, Abscess, Cellulitis, Complicated skin and skin-structure infections
Brief summary
This study will evaluate the safety and efficacy of daptomycin against complicated skin and skin-structure infections in adults
Interventions
DRUGDaptomycin
Sponsors
Novartis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of complicated skin and skin-structure infections (cSSTI) defined as infection normally requiring surgical/local debridement of sufficient severity to warrant hospitalization and intravenous antimicrobial treatment * Infection to be due to Gram-positive bacteria * Hospitalized subjects * Written informed consent * Female patients of childbearing potential must have a negative pregnancy test urine or serum at baseline and must use effective contraception throughout the study period.
Exclusion criteria
* Complicated skin and skin-structure infections of the following categories: * Infected burns * Severely impaired arterial blood supply * Decubitus ulcers * Infected diabetic foot ulcers associated with osteomyelitis * Infected human or animal bites * Perirectal abscess * Necrotising fasciitis or gangrene * Infections expected to require more than 14 days of intravenous antimicrobial therapy * Skin and/or skin structure infection that can be treated by surgery alone * Infections associated with a permanent prosthetic device that will not be removed within 2 days of study enrollment * Uncomplicated skin or soft tissue infection * Documented bacteremia at baseline * Concomitant infection nearby the site of infection at baseline, potentially interfering with the evaluations * Hospitalization for conditions related to rhabdomyolysis * Human immunodeficiency virus (HIV) with cluster of differentiation (CD) \< 200 or \< 14% * Immune function alterations * Lack of sufficient purulent material for culture and Gram test * Systemic or local antibiotic administration with known anti-Gram positive activity in the preceding 48 hours * Complicated skin and soft tissue infections (cSSTI) known or believed to be related to fungal, parasitic or viral infection * Pneumonia * Local or systemic known or suspected allergy to daptomycin * Creatinine clearance \< 30 mL/min * Severe liver damage (Child-Pugh class C) or Alanine transaminase (ALT) and/or Aspartate aminotransferase (AST) \> 3 x Upper limit of normal (ULN) and/or bilirubin \> 1.5 x ULN * Use of any experimental drugs in the preceding 30 days * Severe medical conditions that in the investigator's opinion could counter indicate participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Clinical Success at the Day 7 (D7) and Day 14 (D14) Visit After Treatment Start | at Day 7 and 14 | Primary objective of the study was to evaluate the efficacy of intravenous (IV) daptomycin in the treatment of complicated skin and soft tissue infections (cSSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), as assessed by measuring the clinical success rate achieved at the day 7 and day 14 visit (D7, D14) after treatment start. Clinical success is defined as complete resolution of signs and symptoms of infection, or clinical improvement, i.e. partial resolution of signs and symptoms so that no further antibacterial treatment was required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Assessed as Percentage of Patients With Clinical Success at Day 4 and 10 | At day 4 and 10 | To evaluate the efficacy of intravenous (IV) daptomycin in the treatment of complicated skin and soft tissue infections (cSSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), as assessed by measuring the clinical success rate achieved at the interim visits on day 4 (D4) and day 10 (D10) after treatment start. Clinical success is defined as complete resolution of signs and symptoms of infection, or clinical improvement, i.e. partial resolution of signs and symptoms so that no further antibacterial treatment was required. |
| Efficacy Assessed by Duration of Treatment With Daptomycin Intravenous | At day 14 | — |
| Efficacy Assessed as Success After 4, 7, 10 and 14 Days of Treatment With Daptomycin on Infecting Gram Positive Bacteria | At day 4, 7, 10 and 14 | To evaluate the microbiological efficacy of intravenous (IV) daptomycin in the treatment of complicated skin and soft tissue infections (cSSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), as assessed by measuring the proportion of patients achieving eradication of the Gram-positive baseline organisms at the study visits on D4, D7, D10, and D14. Microbiological success is documented eradication of baseline Gram-positive organism or presumed eradication defined as clinical success and no culture performed because of absence of drainage or other material for culture. |
| Safety Assessed by Hematological and Biochemical Tests, Urinalysis, and Recording and Follow-up of Emerging AE and SAE | At day 14 | — |
| Evaluated Resource Utilization and Calculated Overall Treatment Cost (Including Treatment Period and Follow-up Period) | at day 14 and follow up day i.e. day 30 | — |
| Efficacy Assessed by Time of Resolution of Infection | At day 14 | Time to resolution of signs and symptoms of infection, time to resolution of fever (oral or tympanic temperature ≤37.5°C). |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Daptomycin Intravenous 350 mg of Daptomycin was supplied as sterile lyophilized powder in glass vials. Each vial was to be reconstituted with 7 mL of normal saline or water for injection, to give a 50 mg/mL drug concentration. Daptomycin was to be administered as a 30-minute intravenous infusion, once daily for at least 7 days, at the dose of 4 mg/Kg, up to a maximum of 14 days. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | No longer require therapy | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Daptomycin Intravenous |
|---|---|
| Age, Customized Age 27-88 years | 52 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 52 |
| serious Total, serious adverse events | 4 / 52 |
Outcome results
Primary
Proportion of Participants With Clinical Success at the Day 7 (D7) and Day 14 (D14) Visit After Treatment Start
Primary objective of the study was to evaluate the efficacy of intravenous (IV) daptomycin in the treatment of complicated skin and soft tissue infections (cSSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), as assessed by measuring the clinical success rate achieved at the day 7 and day 14 visit (D7, D14) after treatment start. Clinical success is defined as complete resolution of signs and symptoms of infection, or clinical improvement, i.e. partial resolution of signs and symptoms so that no further antibacterial treatment was required.
Time frame: at Day 7 and 14
Population: Intention to treat (ITT) and safety population: all patients who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daptomycin Intravenous | Proportion of Participants With Clinical Success at the Day 7 (D7) and Day 14 (D14) Visit After Treatment Start | 0 Participants |
Secondary
Efficacy Assessed as Percentage of Patients With Clinical Success at Day 4 and 10
To evaluate the efficacy of intravenous (IV) daptomycin in the treatment of complicated skin and soft tissue infections (cSSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), as assessed by measuring the clinical success rate achieved at the interim visits on day 4 (D4) and day 10 (D10) after treatment start. Clinical success is defined as complete resolution of signs and symptoms of infection, or clinical improvement, i.e. partial resolution of signs and symptoms so that no further antibacterial treatment was required.
Time frame: At day 4 and 10
Secondary
Efficacy Assessed as Success After 4, 7, 10 and 14 Days of Treatment With Daptomycin on Infecting Gram Positive Bacteria
To evaluate the microbiological efficacy of intravenous (IV) daptomycin in the treatment of complicated skin and soft tissue infections (cSSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), as assessed by measuring the proportion of patients achieving eradication of the Gram-positive baseline organisms at the study visits on D4, D7, D10, and D14. Microbiological success is documented eradication of baseline Gram-positive organism or presumed eradication defined as clinical success and no culture performed because of absence of drainage or other material for culture.
Time frame: At day 4, 7, 10 and 14
Secondary
Efficacy Assessed by Duration of Treatment With Daptomycin Intravenous
Time frame: At day 14
Secondary
Efficacy Assessed by Time of Resolution of Infection
Time to resolution of signs and symptoms of infection, time to resolution of fever (oral or tympanic temperature ≤37.5°C).
Time frame: At day 14
Secondary
Evaluated Resource Utilization and Calculated Overall Treatment Cost (Including Treatment Period and Follow-up Period)
Time frame: at day 14 and follow up day i.e. day 30
Secondary
Safety Assessed by Hematological and Biochemical Tests, Urinalysis, and Recording and Follow-up of Emerging AE and SAE
Time frame: At day 14