Bacterial Infections, Diabetic Foot, Osteomyelitis
Conditions
Keywords
Diabetic foot infection, Osteomyelitis, Diabetes Complications, Foot ulcer, Skin infection
Brief summary
The purpose of this study was to look at the safety and effectiveness of a once-daily dose of tigecycline compared to ertapenem for the treatment of diabetic foot infections. The co-primary efficacy endpoints were not met.
Interventions
DRUGTigecycline
150 mg Tigecycline once-daily IV infusion for up to 28 days, or 42 days for the substudy wth osteomyelitis
DRUGErtapenem
Ertapenem 1g IV infusion every 24 hours +/- vancomycin depending on culture results and at the discretion of investigator (for coverage of Methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci (CNS) or enterococci coverage).
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
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
Main inclusion criteria: * Men and women aged 18 or older with diabetes and a qualifying foot infection. People with evidence of a diabetic foot infection with osteomyelitis may qualify for the osteomyelitis substudy arm. Main
Exclusion criteria
* People with additional significant disease, infection with resistant pathogens, contraindication, or hypersensitivity to any test article or related antibiotic.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Clinical Response of Cure Vs. Failure. | Test of cure visit (TOC): Assessed at least 12 days post last dose | Cure: Recovery so no added antibiotic therapy. Failure: Added antibiotic therapy for no response or worsening after improvement, new purulence, \>120% doses, non-routine surgical treatment or death related to Diabetic Foot Infections (DFI) \> 48 hrs. |
| Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate. | Test of cure visit (TOC): Assessed at least 12 days post last dose | Cure: Recovery so no added antibiotic therapy. Failure: Added antibiotic therapy for no response or worsening after improvement, new purulence, \>120% doses, non-routine surgical treatment or death related to DFI \> 48 hrs. Indeterminate: Lost to follow-up, death\<48 hours or noninfection related. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Clinical Response of Cure Vs. Failure Assessed at Least 25 - 27 Weeks Post Last Dose. | Test of cure visit (TOC): Assessed at least 25 - 27 weeks post last dose | Cure: Recovery so no added antibiotic therapy. Failure: Added antibiotic therapy for no response or worsening after improvement, new purulence, \>120% doses, non-routine surgical treatment or death related to DFI \> 48 hrs. |
| Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose. | Test of cure visit (TOC): Assessed at least 25 - 27 weeks post last dose | Cure: Recovery so no added antibiotic therapy. Failure: Added antibiotic therapy for no response or worsening after improvement, new purulence, \>120% doses, non-routine surgical treatment or death related to DFI \> 48 hrs. Indeterminate: Lost to follow-up, death\<48 hours or noninfection related. |
| Number of Patients With Microbiologic Response of Eradication. | Test of cure visit (TOC): Assessed at least 12 days post last dose | Eradication defined as: no pathogen is present in the repeat culture from the original site of infection, or a clinical response of the cure precludes the availability of a specimen for culture. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Croatia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, India, Italy, Latvia, Lithuania, Mexico, Panama, Peru, Poland, Portugal, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Patients were recruited worldwide from January 2007 to February 2009.
Pre-assignment details
Patients were screened for up to 24 hours.
Participants by arm
| Arm | Count |
|---|---|
| Tigecycline Tigecycline 150 mg IV infusion every 24 hours | 553 |
| Ertapenem Ertapenem 1g IV infusion every 24 hours +/- vancomycin depending on culture results and at the discretion of investigator (for coverage of Methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci (CNS) or enterococci coverage). | 508 |
| Total | 1,061 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 53 | 28 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 21 | 21 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Most due to osteomylitis status | 31 | 20 |
| Overall Study | Physician Decision | 5 | 2 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 18 | 4 |
Baseline characteristics
| Characteristic | Tigecycline | Ertapenem | Total |
|---|---|---|---|
| Age Continuous | 59.36 years STANDARD_DEVIATION 12.04 | 58.75 years STANDARD_DEVIATION 11.7 | 59.07 years STANDARD_DEVIATION 11.88 |
| Sex: Female, Male Female | 199 Participants | 165 Participants | 364 Participants |
| Sex: Female, Male Male | 354 Participants | 343 Participants | 697 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 406 / — | 292 / — |
| serious Total, serious adverse events | 79 / — | 62 / — |
Outcome results
Primary
Number of Patients With Clinical Response of Cure Vs. Failure.
Cure: Recovery so no added antibiotic therapy. Failure: Added antibiotic therapy for no response or worsening after improvement, new purulence, \>120% doses, non-routine surgical treatment or death related to Diabetic Foot Infections (DFI) \> 48 hrs.
Time frame: Test of cure visit (TOC): Assessed at least 12 days post last dose
Population: Clinically evaluable population without osteomyelitis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure. | Cure | 316 patients |
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure. | Failure | 92 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure. | Cure | 334 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure. | Failure | 71 patients |
Comparison: Analysis provided for Cure95% CI: [-11, 0.1]
Primary
Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate.
Cure: Recovery so no added antibiotic therapy. Failure: Added antibiotic therapy for no response or worsening after improvement, new purulence, \>120% doses, non-routine surgical treatment or death related to DFI \> 48 hrs. Indeterminate: Lost to follow-up, death\<48 hours or noninfection related.
Time frame: Test of cure visit (TOC): Assessed at least 12 days post last dose
Population: Clinical modified intent to treat population without osteomyelitis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate. | Cure | 340 patients |
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate. | Failure | 117 patients |
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate. | Indeterminate | 19 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate. | Cure | 363 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate. | Failure | 86 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate. | Indeterminate | 17 patients |
Comparison: Analysis provided for Cure95% CI: [-12.3, -1.1]
Secondary
Number of Patients With Clinical Response of Cure Vs. Failure Assessed at Least 25 - 27 Weeks Post Last Dose.
Cure: Recovery so no added antibiotic therapy. Failure: Added antibiotic therapy for no response or worsening after improvement, new purulence, \>120% doses, non-routine surgical treatment or death related to DFI \> 48 hrs.
Time frame: Test of cure visit (TOC): Assessed at least 25 - 27 weeks post last dose
Population: Clinically evaluable population with osteomyelitis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure Assessed at Least 25 - 27 Weeks Post Last Dose. | Cure | 12 patients |
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure Assessed at Least 25 - 27 Weeks Post Last Dose. | Failure | 26 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure Assessed at Least 25 - 27 Weeks Post Last Dose. | Cure | 13 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure Assessed at Least 25 - 27 Weeks Post Last Dose. | Failure | 11 patients |
Secondary
Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose.
Cure: Recovery so no added antibiotic therapy. Failure: Added antibiotic therapy for no response or worsening after improvement, new purulence, \>120% doses, non-routine surgical treatment or death related to DFI \> 48 hrs. Indeterminate: Lost to follow-up, death\<48 hours or noninfection related.
Time frame: Test of cure visit (TOC): Assessed at least 25 - 27 weeks post last dose
Population: Clinical modified intent to treat population with osteomyelitis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose. | Cure | 19 patients |
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose. | Failure | 27 patients |
| Tigecycline | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose. | Indeterminate | 7 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose. | Cure | 21 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose. | Failure | 12 patients |
| Ertapenem | Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose. | Indeterminate | 0 patients |
Secondary
Number of Patients With Microbiologic Response of Eradication.
Eradication defined as: no pathogen is present in the repeat culture from the original site of infection, or a clinical response of the cure precludes the availability of a specimen for culture.
Time frame: Test of cure visit (TOC): Assessed at least 12 days post last dose
Population: Microbiologically evaluable population without osteomyelitis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tigecycline | Number of Patients With Microbiologic Response of Eradication. | 209 patients |
| Ertapenem | Number of Patients With Microbiologic Response of Eradication. | 229 patients |
95% CI: [-13.6, 1]