Trial Outcomes & Findings for Study to Compare Efficacy and Safety of Daptomycin in Elderly Patients With Complicated Skin and Soft Tissue Infections (NCT NCT01184872)
NCT ID: NCT01184872
Last Updated: 2012-07-13
Results Overview
Success: Clinically significant signs and symptoms associated with the skin infection present at the pre-treatment infection site resolved (cure), or improved without need of further antibacterial therapy. Failure: Persistence or progression of signs and symptoms or development of new clinical signs and symptoms at the infection site, or concomitant antibacterial therapy with activity against isolated organisms, or treatment duration longer than pre-specified, or switch back to intravenous therapy due to relapse, or requirement of a major surgical procedure as adjunct or follow-up therapy.
COMPLETED
PHASE3
120 participants
Baseline and 7 to 14 days after end of therapy
2012-07-13
Participant Flow
Participant milestones
| Measure |
Daptomycin
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Overall Study
STARTED
|
81
|
39
|
|
Overall Study
Safety Set
|
80
|
40
|
|
Overall Study
Clinical Evaluable Set (CES)
|
73
|
30
|
|
Overall Study
Microbiologically Evaluable Set (MES)
|
65
|
27
|
|
Overall Study
COMPLETED
|
71
|
31
|
|
Overall Study
NOT COMPLETED
|
10
|
8
|
Reasons for withdrawal
| Measure |
Daptomycin
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
4
|
|
Overall Study
Unsatisfactory therapeutic effect
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Administrative problems
|
1
|
1
|
|
Overall Study
Protocol deviation
|
1
|
0
|
Baseline Characteristics
Study to Compare Efficacy and Safety of Daptomycin in Elderly Patients With Complicated Skin and Soft Tissue Infections
Baseline characteristics by cohort
| Measure |
Daptomycin
n=81 Participants
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
n=39 Participants
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
74.63 years
STANDARD_DEVIATION 6.331 • n=5 Participants
|
75.28 years
STANDARD_DEVIATION 5.515 • n=7 Participants
|
74.84 years
STANDARD_DEVIATION 6.063 • n=5 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 7 to 14 days after end of therapyPopulation: The clinically evaluable population was used for the efficacy analysis. It included all patients who met the criteria for complicated skin and soft tissue, had no substantive protocol deviation, had a sponsor clinical response assessment of "success" or "failure" at the assessment visit, and had a specified baseline primary site of infection.
Success: Clinically significant signs and symptoms associated with the skin infection present at the pre-treatment infection site resolved (cure), or improved without need of further antibacterial therapy. Failure: Persistence or progression of signs and symptoms or development of new clinical signs and symptoms at the infection site, or concomitant antibacterial therapy with activity against isolated organisms, or treatment duration longer than pre-specified, or switch back to intravenous therapy due to relapse, or requirement of a major surgical procedure as adjunct or follow-up therapy.
Outcome measures
| Measure |
Daptomycin
n=73 Participants
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
n=30 Participants
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Number of Patients With Clinical Success at the Test-Of-Cure (TOC) Visit
Success
|
65 participants
|
25 participants
|
|
Number of Patients With Clinical Success at the Test-Of-Cure (TOC) Visit
Failure
|
8 participants
|
5 participants
|
SECONDARY outcome
Timeframe: Baseline and 7 to 14 days after end of therapyPopulation: Population analyzed consisted of patients from the clinically evaluable population who had independent microbiological assessments.
Microbiological Success: All infecting Gram-positive pathogens isolated at baseline were eradicated or presumed to be eradicated at the Test-of-Cure (TOC) evaluation and a super infecting pathogen was not isolated either prior to or at the TOC evaluation. Microbiological Failure: Persistence or relapse / re-infection of one or more infecting Gram-positive pathogens or isolation of a super infecting pathogen prior to or at the TOC evaluation.
Outcome measures
| Measure |
Daptomycin
n=65 Participants
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
n=27 Participants
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Number of Participants With Microbiological Response at Test-of-Cure (TOC) Visit
Failure
|
11 participants
|
4 participants
|
|
Number of Participants With Microbiological Response at Test-of-Cure (TOC) Visit
Success
|
54 participants
|
23 participants
|
SECONDARY outcome
Timeframe: Up to 28 daysPopulation: The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned at randomization.
Duration of treatment is the interval from first to last intravenous (i.v.) administration. It was preferable that a patient complete the whole antibiotic treatment with the randomized i.v. study drug only. Duration of treatment in patients with bacteremia could be extended up to 28 days.
Outcome measures
| Measure |
Daptomycin
n=81 Participants
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
n=39 Participants
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Duration of Treatment (Intravenous)
|
7.8 Days
Standard Deviation 3.42
|
7.3 Days
Standard Deviation 2.42
|
SECONDARY outcome
Timeframe: Up to 28 daysPopulation: The Full Analysis set (FAS) comprised all patients to whom study treatment had been assigned at randomization.
Duration of treatment is the interval from first to last intravenous (i.v.) or to last oral administration if patients switched to an oral antibiotic therapy. It was preferable that a patient complete the whole antibiotic treatment with the randomized i.v. study drug only. Duration of treatment in patients with bacteremia could be extended up to 28 days.
Outcome measures
| Measure |
Daptomycin
n=81 Participants
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
n=39 Participants
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Duration of Treatment (Intravenous and Oral)
intravenous + oral
|
8.7 Days
Standard Deviation 4.9
|
9.6 Days
Standard Deviation 5.4
|
|
Duration of Treatment (Intravenous and Oral)
intravenous only
|
7.8 Days
Standard Deviation 3.4
|
7.3 Days
Standard Deviation 2.4
|
SECONDARY outcome
Timeframe: Continuously from baseline up to 28 days after end of antibiotic treatment.Population: The safety set included all patients who received at least one dose of study medication and who had at least one post-baseline safety assessment.
Outcome measures
| Measure |
Daptomycin
n=80 Participants
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
n=40 Participants
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Number of Patients With Adverse Events, Serious Adverse Events and Death
Adverse Events
|
50 participants
|
26 participants
|
|
Number of Patients With Adverse Events, Serious Adverse Events and Death
Serious Adverse Events
|
7 participants
|
4 participants
|
|
Number of Patients With Adverse Events, Serious Adverse Events and Death
Death
|
0 participants
|
0 participants
|
Adverse Events
Daptomycin
Vancomycin or Semi-Synthetic Penicillins (SSPs)
Serious adverse events
| Measure |
Daptomycin
n=80 participants at risk
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
n=40 participants at risk
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/80
|
2.5%
1/40
|
|
General disorders
Necrosis
|
1.2%
1/80
|
0.00%
0/40
|
|
Infections and infestations
Klebsiella infection
|
1.2%
1/80
|
0.00%
0/40
|
|
Infections and infestations
Pneumonia
|
1.2%
1/80
|
0.00%
0/40
|
|
Investigations
Blood creatine phosphokinase increased
|
1.2%
1/80
|
0.00%
0/40
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Nasopharyngeal cancer recurrent
|
1.2%
1/80
|
0.00%
0/40
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
1.2%
1/80
|
0.00%
0/40
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/80
|
2.5%
1/40
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.00%
0/80
|
2.5%
1/40
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/80
|
2.5%
1/40
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/80
|
2.5%
1/40
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.2%
1/80
|
0.00%
0/40
|
|
Vascular disorders
Thrombosis
|
1.2%
1/80
|
0.00%
0/40
|
Other adverse events
| Measure |
Daptomycin
n=80 participants at risk
Patients with bacteremia: Daptomycin 6 mg/Kg intravenous once daily for at least 5 days and up to 28 days.
Patients without bacteremia: Daptomycin 4 mg/Kg intravenous once daily for at least 5 days and up to 14 days.
|
Vancomycin or Semi-Synthetic Penicillins (SSPs)
n=40 participants at risk
Patients with bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 4 hours for at least 5 days and up to 28 days.
Patients without bacteremia: Vancomycin 1 g intravenous twice daily or Semi-Synthetic Penicillins 2 g intravenous every 6 hours for at least 5 days and up to 14 days.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
6.2%
5/80
|
5.0%
2/40
|
|
General disorders
Hyperthermia
|
13.8%
11/80
|
7.5%
3/40
|
|
Investigations
Blood creatine phosphokinase increased
|
6.2%
5/80
|
2.5%
1/40
|
|
Investigations
Blood creatinine increased
|
1.2%
1/80
|
5.0%
2/40
|
|
Investigations
Blood pressure increased
|
6.2%
5/80
|
5.0%
2/40
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/80
|
5.0%
2/40
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.0%
4/80
|
2.5%
1/40
|
|
Vascular disorders
Hypertension
|
7.5%
6/80
|
12.5%
5/40
|
Additional Information
Study Director
Novartis Pharmaceutical
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER