Trial Outcomes & Findings for Study Evaluating the Safety and Efficacy of a Once-daily Dose of Tigecycline vs Ertapenem in Diabetic Foot Infections (DFI) With a Substudy in Patients With Diabetic Foot Infections Complicated by Osteomyelitis. (NCT NCT00366249)
NCT ID: NCT00366249
Last Updated: 2010-04-28
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1061 participants
Primary outcome timeframe
Test of cure visit (TOC): Assessed at least 12 days post last dose
Results posted on
2010-04-28
Participant Flow
Patients were recruited worldwide from January 2007 to February 2009.
Patients were screened for up to 24 hours.
Participant milestones
| Measure |
Tigecycline
Tigecycline 150 mg IV infusion every 24 hours
|
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).
|
|---|---|---|
|
Overall Study
STARTED
|
553
|
508
|
|
Overall Study
COMPLETED
|
422
|
430
|
|
Overall Study
NOT COMPLETED
|
131
|
78
|
Reasons for withdrawal
| Measure |
Tigecycline
Tigecycline 150 mg IV infusion every 24 hours
|
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).
|
|---|---|---|
|
Overall Study
Adverse Event
|
53
|
28
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Physician Decision
|
5
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Protocol Violation
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
18
|
4
|
|
Overall Study
Lack of Efficacy
|
21
|
21
|
|
Overall Study
Most due to osteomylitis status
|
31
|
20
|
Baseline Characteristics
Study Evaluating the Safety and Efficacy of a Once-daily Dose of Tigecycline vs Ertapenem in Diabetic Foot Infections (DFI) With a Substudy in Patients With Diabetic Foot Infections Complicated by Osteomyelitis.
Baseline characteristics by cohort
| Measure |
Tigecycline
n=553 Participants
Tigecycline 150 mg IV infusion every 24 hours
|
Ertapenem
n=508 Participants
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).
|
Total
n=1061 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
59.36 years
STANDARD_DEVIATION 12.04 • n=5 Participants
|
58.75 years
STANDARD_DEVIATION 11.70 • n=7 Participants
|
59.07 years
STANDARD_DEVIATION 11.88 • n=5 Participants
|
|
Sex: Female, Male
Female
|
199 Participants
n=5 Participants
|
165 Participants
n=7 Participants
|
364 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
354 Participants
n=5 Participants
|
343 Participants
n=7 Participants
|
697 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Test of cure visit (TOC): Assessed at least 12 days post last dosePopulation: Clinically evaluable population without osteomyelitis.
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.
Outcome measures
| Measure |
Tigecycline
n=408 Participants
Tigecycline 150 mg IV infusion every 24 hours
|
Ertapenem
n=405 Participants
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).
|
|---|---|---|
|
Number of Patients With Clinical Response of Cure Vs. Failure.
Cure
|
316 patients
|
334 patients
|
|
Number of Patients With Clinical Response of Cure Vs. Failure.
Failure
|
92 patients
|
71 patients
|
PRIMARY outcome
Timeframe: Test of cure visit (TOC): Assessed at least 12 days post last dosePopulation: Clinical modified intent to treat population without osteomyelitis.
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.
Outcome measures
| Measure |
Tigecycline
n=476 Participants
Tigecycline 150 mg IV infusion every 24 hours
|
Ertapenem
n=466 Participants
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).
|
|---|---|---|
|
Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate.
Cure
|
340 patients
|
363 patients
|
|
Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate.
Failure
|
117 patients
|
86 patients
|
|
Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate.
Indeterminate
|
19 patients
|
17 patients
|
SECONDARY outcome
Timeframe: Test of cure visit (TOC): Assessed at least 25 - 27 weeks post last dosePopulation: Clinically evaluable population with osteomyelitis.
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.
Outcome measures
| Measure |
Tigecycline
n=38 Participants
Tigecycline 150 mg IV infusion every 24 hours
|
Ertapenem
n=24 Participants
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).
|
|---|---|---|
|
Number of Patients With Clinical Response of Cure Vs. Failure Assessed at Least 25 - 27 Weeks Post Last Dose.
Cure
|
12 patients
|
13 patients
|
|
Number of Patients With Clinical Response of Cure Vs. Failure Assessed at Least 25 - 27 Weeks Post Last Dose.
Failure
|
26 patients
|
11 patients
|
SECONDARY outcome
Timeframe: Test of cure visit (TOC): Assessed at least 25 - 27 weeks post last dosePopulation: Clinical modified intent to treat population with osteomyelitis.
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.
Outcome measures
| Measure |
Tigecycline
n=53 Participants
Tigecycline 150 mg IV infusion every 24 hours
|
Ertapenem
n=33 Participants
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).
|
|---|---|---|
|
Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose.
Cure
|
19 patients
|
21 patients
|
|
Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose.
Failure
|
27 patients
|
12 patients
|
|
Number of Patients With Clinical Response of Cure Vs. Failure/Indeterminate Assessed at Least 25 - 27 Weeks Post Last Dose.
Indeterminate
|
7 patients
|
0 patients
|
SECONDARY outcome
Timeframe: Test of cure visit (TOC): Assessed at least 12 days post last dosePopulation: Microbiologically evaluable population without osteomyelitis.
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.
Outcome measures
| Measure |
Tigecycline
n=316 Participants
Tigecycline 150 mg IV infusion every 24 hours
|
Ertapenem
n=317 Participants
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).
|
|---|---|---|
|
Number of Patients With Microbiologic Response of Eradication.
|
209 patients
|
229 patients
|
Adverse Events
Tigecycline
Serious events: 79 serious events
Other events: 406 other events
Deaths: 0 deaths
Ertapenem
Serious events: 62 serious events
Other events: 292 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tigecycline
Tigecycline 150 mg IV infusion every 24 hours
|
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).
|
|---|---|---|
|
General disorders
Abdominal pain
|
0.18%
1/553
|
0.00%
0/508
|
|
General disorders
Abscess
|
0.90%
5/553
|
0.00%
0/508
|
|
General disorders
Accidental injury
|
0.00%
0/553
|
0.20%
1/508
|
|
General disorders
Allergic reaction
|
0.18%
1/553
|
0.00%
0/508
|
|
General disorders
Asthenia
|
0.00%
0/553
|
0.20%
1/508
|
|
General disorders
Carcinoma
|
0.00%
0/553
|
0.20%
1/508
|
|
General disorders
Cellulitis
|
0.18%
1/553
|
0.00%
0/508
|
|
General disorders
Chest pain
|
0.36%
2/553
|
0.20%
1/508
|
|
General disorders
Fever
|
0.72%
4/553
|
0.00%
0/508
|
|
General disorders
Gangrene
|
0.54%
3/553
|
0.39%
2/508
|
|
General disorders
Infection
|
1.6%
9/553
|
3.1%
16/508
|
|
General disorders
Pain
|
0.00%
0/553
|
0.20%
1/508
|
|
General disorders
Sepsis
|
0.18%
1/553
|
0.20%
1/508
|
|
General disorders
Septic shock
|
0.18%
1/553
|
0.00%
0/508
|
|
General disorders
Sudden death
|
0.18%
1/553
|
0.00%
0/508
|
|
Vascular disorders
Arterial thrombosis
|
0.18%
1/553
|
0.20%
1/508
|
|
Cardiac disorders
Atrial fibrillation
|
0.36%
2/553
|
0.00%
0/508
|
|
Cardiac disorders
Bundle branch block
|
0.00%
0/553
|
0.20%
1/508
|
|
Cardiac disorders
Cardiomegaly
|
0.00%
0/553
|
0.20%
1/508
|
|
Cardiac disorders
Cerebral ischemia
|
0.18%
1/553
|
0.00%
0/508
|
|
Cardiac disorders
Cerebrovascular accident
|
0.00%
0/553
|
0.39%
2/508
|
|
Cardiac disorders
Congestive heart failure
|
0.18%
1/553
|
0.39%
2/508
|
|
Cardiac disorders
Coronary artery disorder
|
0.18%
1/553
|
0.00%
0/508
|
|
Vascular disorders
Deep vein thrombosis
|
0.18%
1/553
|
0.00%
0/508
|
|
Cardiac disorders
Heart arrest
|
0.18%
1/553
|
0.00%
0/508
|
|
Cardiac disorders
Heart failure
|
0.00%
0/553
|
0.20%
1/508
|
|
Vascular disorders
Hemorrhage
|
0.00%
0/553
|
0.20%
1/508
|
|
Cardiac disorders
Myocardial infarct
|
0.72%
4/553
|
0.00%
0/508
|
|
Cardiac disorders
Occlusion
|
0.18%
1/553
|
0.39%
2/508
|
|
Vascular disorders
Peripheral gangrene
|
0.36%
2/553
|
0.00%
0/508
|
|
Vascular disorders
Peripheral vascular disorder
|
0.18%
1/553
|
0.39%
2/508
|
|
Vascular disorders
Pulmonary embolus
|
0.18%
1/553
|
0.00%
0/508
|
|
Cardiac disorders
Shock
|
0.36%
2/553
|
0.00%
0/508
|
|
Cardiac disorders
Syncope
|
0.18%
1/553
|
0.39%
2/508
|
|
Cardiac disorders
Tachycardia
|
0.18%
1/553
|
0.00%
0/508
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/553
|
0.20%
1/508
|
|
Vascular disorders
Thrombosis
|
0.00%
0/553
|
0.20%
1/508
|
|
Vascular disorders
Vasculitis
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Cholelithiasis
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Cirrhosis of liver
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Diarrhea
|
0.18%
1/553
|
0.20%
1/508
|
|
Gastrointestinal disorders
Gastritis
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Gastrointestinal hemorrhage
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Ileus
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Liver damage
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Nausea
|
1.1%
6/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Stomach atony
|
0.18%
1/553
|
0.00%
0/508
|
|
Gastrointestinal disorders
Vomiting
|
1.1%
6/553
|
0.00%
0/508
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.18%
1/553
|
0.00%
0/508
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/553
|
0.20%
1/508
|
|
Metabolism and nutrition disorders
Acidosis
|
0.18%
1/553
|
0.00%
0/508
|
|
Metabolism and nutrition disorders
Alkaline phosphatase increased
|
0.00%
0/553
|
0.20%
1/508
|
|
Metabolism and nutrition disorders
Dehydration
|
0.18%
1/553
|
0.00%
0/508
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/553
|
0.20%
1/508
|
|
Metabolism and nutrition disorders
Healing abnormal
|
0.18%
1/553
|
0.20%
1/508
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.54%
3/553
|
0.00%
0/508
|
|
Metabolism and nutrition disorders
Hypoglycemic reaction
|
0.00%
0/553
|
0.20%
1/508
|
|
Metabolism and nutrition disorders
Lipase increased
|
0.18%
1/553
|
0.00%
0/508
|
|
Musculoskeletal and connective tissue disorders
Arthrosis
|
0.18%
1/553
|
0.20%
1/508
|
|
Musculoskeletal and connective tissue disorders
Osteomyelitis
|
3.1%
17/553
|
0.98%
5/508
|
|
Musculoskeletal and connective tissue disorders
Pyogenic arthritis
|
0.18%
1/553
|
0.00%
0/508
|
|
Nervous system disorders
Convulsion
|
0.36%
2/553
|
0.79%
4/508
|
|
Nervous system disorders
Hallucinations
|
0.00%
0/553
|
0.20%
1/508
|
|
Nervous system disorders
Hypesthesia
|
0.00%
0/553
|
0.20%
1/508
|
|
Nervous system disorders
Mental status changes
|
0.18%
1/553
|
0.20%
1/508
|
|
Nervous system disorders
Neuropathy
|
0.00%
0/553
|
0.20%
1/508
|
|
Nervous system disorders
Somnolence
|
0.18%
1/553
|
0.00%
0/508
|
|
Nervous system disorders
Stupor
|
0.00%
0/553
|
0.20%
1/508
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/553
|
0.20%
1/508
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonia
|
0.00%
0/553
|
0.20%
1/508
|
|
Respiratory, thoracic and mediastinal disorders
Cough increased
|
0.18%
1/553
|
0.00%
0/508
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.36%
2/553
|
0.00%
0/508
|
|
Respiratory, thoracic and mediastinal disorders
Lung edema
|
0.18%
1/553
|
0.00%
0/508
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/553
|
0.20%
1/508
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.36%
2/553
|
0.20%
1/508
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.18%
1/553
|
0.20%
1/508
|
|
Skin and subcutaneous tissue disorders
Skin necrosis
|
0.72%
4/553
|
0.59%
3/508
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.36%
2/553
|
0.39%
2/508
|
|
Skin and subcutaneous tissue disorders
Vesiculobullous rash
|
0.00%
0/553
|
0.20%
1/508
|
|
Renal and urinary disorders
Acute kidney failure
|
0.18%
1/553
|
0.00%
0/508
|
|
Renal and urinary disorders
Kidney function abnormal
|
0.00%
0/553
|
0.39%
2/508
|
|
Renal and urinary disorders
Urinary tract infection
|
0.18%
1/553
|
0.00%
0/508
|
|
General disorders
Local reaction to procedure
|
0.00%
0/553
|
0.20%
1/508
|
|
Cardiac disorders
Left heart failure
|
0.36%
2/553
|
0.00%
0/508
|
|
Vascular disorders
Vascular disorder general
|
0.18%
1/553
|
0.20%
1/508
|
Other adverse events
| Measure |
Tigecycline
Tigecycline 150 mg IV infusion every 24 hours
|
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).
|
|---|---|---|
|
General disorders
Abdominal pain
|
3.6%
20/553
|
2.2%
11/508
|
|
General disorders
Asthenia
|
3.4%
19/553
|
1.6%
8/508
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory system general
|
5.8%
32/553
|
5.7%
29/508
|
|
General disorders
Fever
|
4.9%
27/553
|
3.7%
19/508
|
|
General disorders
Headache
|
4.7%
26/553
|
3.9%
20/508
|
|
Skin and subcutaneous tissue disorders
Skin and appendages general
|
7.8%
43/553
|
5.5%
28/508
|
|
General disorders
Pain
|
4.5%
25/553
|
3.3%
17/508
|
|
Renal and urinary disorders
Urogenital general
|
4.3%
24/553
|
5.3%
27/508
|
|
Cardiac disorders
Hypertension
|
6.5%
36/553
|
7.9%
40/508
|
|
Gastrointestinal disorders
Diarrhea
|
13.6%
75/553
|
10.0%
51/508
|
|
Gastrointestinal disorders
Dyspepsia
|
3.4%
19/553
|
1.2%
6/508
|
|
Gastrointestinal disorders
Nausea
|
41.0%
227/553
|
9.1%
46/508
|
|
Gastrointestinal disorders
Vomiting
|
27.3%
151/553
|
4.9%
25/508
|
|
Blood and lymphatic system disorders
Anemia
|
2.5%
14/553
|
3.5%
18/508
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
9.0%
50/553
|
4.7%
24/508
|
|
Metabolism and nutrition disorders
Serum glutamic oxaloacetic transaminase (SGOT) increased
|
3.6%
20/553
|
4.1%
21/508
|
|
Metabolism and nutrition disorders
Serum glutamic pyruvic transaminase (SGPT) increased
|
3.4%
19/553
|
3.9%
20/508
|
|
Musculoskeletal and connective tissue disorders
Osteomyelitis
|
4.5%
25/553
|
2.4%
12/508
|
|
Nervous system disorders
Dizziness
|
3.1%
17/553
|
2.0%
10/508
|
|
Nervous system disorders
Insomnia
|
3.3%
18/553
|
0.98%
5/508
|
|
General disorders
Infection
|
2.2%
12/553
|
3.7%
19/508
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER