Trial Outcomes & Findings for Efficacy and Safety of Daptomycin Versus Vancomycin or Teicoplanin for Treatment of Complicated Skin and Soft Tissue Infections (NCT NCT00430937)
NCT ID: NCT00430937
Last Updated: 2012-07-16
Results Overview
Success: Total resolution of clinically significant signs and symptoms of the infection site (cure) or improvement to such a level that no further antibacterial therapy was required (improvement). Failure: Persistence or progression of signs and symptoms after at least 3 days of study therapy, or development of new signs and symptoms at the infection site, or concomitant or additional antibacterial therapy with documented activity against isolated organisms, or a treatment duration greater than 14 days, or requirement of a major surgical procedure as adjunct or follow-up therapy.
TERMINATED
PHASE3
194 participants
Baseline to TOC Visit (7-14 days after end of treatment) up to 4 weeks
2012-07-16
Participant Flow
194 participants were randomized; 5 participants were not exposed to study drug by mistake; therefore, only 189 participants received study drug.
Participant milestones
| Measure |
Daptomycin
Daptomycin 4 mg/kg intravenous (i.v.) once daily
|
Pooled Comparator
Vancomycin 1 g intravenous (i.v.) twice daily or Teicoplanin 400 mg i.v. once daily following a loading dose of 400 mg administered at 0, 12 and 24 hours on day one.
|
|---|---|---|
|
Overall Study
STARTED
|
97
|
92
|
|
Overall Study
COMPLETED
|
70
|
64
|
|
Overall Study
NOT COMPLETED
|
27
|
28
|
Reasons for withdrawal
| Measure |
Daptomycin
Daptomycin 4 mg/kg intravenous (i.v.) once daily
|
Pooled Comparator
Vancomycin 1 g intravenous (i.v.) twice daily or Teicoplanin 400 mg i.v. once daily following a loading dose of 400 mg administered at 0, 12 and 24 hours on day one.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
8
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
6
|
6
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
|
Overall Study
Protocol Violation
|
3
|
2
|
|
Overall Study
Lack of Efficacy
|
6
|
5
|
|
Overall Study
Inappropriate enrollment
|
2
|
1
|
|
Overall Study
Administrative reasons
|
1
|
0
|
|
Overall Study
Protocol discontinuation criteria met
|
1
|
2
|
|
Overall Study
Unable to classify
|
0
|
1
|
Baseline Characteristics
Efficacy and Safety of Daptomycin Versus Vancomycin or Teicoplanin for Treatment of Complicated Skin and Soft Tissue Infections
Baseline characteristics by cohort
| Measure |
Daptomycin
n=97 Participants
Daptomycin 4 mg/kg intravenous (i.v.) once daily
|
Pooled Comparator
n=92 Participants
Vancomycin 1 g intravenous (i.v.) twice daily or Teicoplanin 400 mg i.v. once daily following a loading dose of 400 mg administered at 0, 12 and 24 hours on day one.
|
Total
n=189 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
< 65 years
|
62 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
123 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
35 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
61 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
112 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to TOC Visit (7-14 days after end of treatment) up to 4 weeksPopulation: The clinically evaluable population was used for the efficacy analysis. It included all patients who met the criteria for cSSTI as listed in the Protocol, 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: Total resolution of clinically significant signs and symptoms of the infection site (cure) or improvement to such a level that no further antibacterial therapy was required (improvement). Failure: Persistence or progression of signs and symptoms after at least 3 days of study therapy, or development of new signs and symptoms at the infection site, or concomitant or additional antibacterial therapy with documented activity against isolated organisms, or a treatment duration greater than 14 days, or requirement of a major surgical procedure as adjunct or follow-up therapy.
Outcome measures
| Measure |
Daptomycin
n=58 Participants
Daptomycin 4 mg/kg intravenous (i.v.) once daily
|
Pooled Comparator
n=47 Participants
Vancomycin 1 g intravenous (i.v.) twice daily or Teicoplanin 400 mg i.v. once daily following a loading dose of 400 mg administered at 0, 12 and 24 hours on day one.
|
|---|---|---|
|
Clinical Success as Measured by Comparing the Participants Signs and Symptoms at the "Test of Cure" (TOC) Visit to Those Recorded at Study Baseline in the Clinically Evaluable Population.
Clinical Success
|
53 Participants
|
41 Participants
|
|
Clinical Success as Measured by Comparing the Participants Signs and Symptoms at the "Test of Cure" (TOC) Visit to Those Recorded at Study Baseline in the Clinically Evaluable Population.
Clinical Failure
|
5 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline to TOC Visit (7-14 days after end of treatment) up to 4 weeksPopulation: Population analyzed consisted of patients from the clinically evaluable population who had microbiological assessments.
Microbiological Success: All infecting Gram-positive pathogens isolated at baseline were eradicated at the TOC evaluation and a superinfecting pathogen was not isolated either prior to or at the TOC evaluation. Microbiological Failure: Persistence of one or more infecting Gram-positive pathogens or isolation of a superinfecting pathogen prior to or at the TOC evaluation.
Outcome measures
| Measure |
Daptomycin
n=57 Participants
Daptomycin 4 mg/kg intravenous (i.v.) once daily
|
Pooled Comparator
n=43 Participants
Vancomycin 1 g intravenous (i.v.) twice daily or Teicoplanin 400 mg i.v. once daily following a loading dose of 400 mg administered at 0, 12 and 24 hours on day one.
|
|---|---|---|
|
Microbiological Efficacy Measured by the Number of Participants Achieving Bacteriological Eradication of Gram-positive Baseline Pathogens at the TOC Visit.
Microbiological Success
|
56 Participants
|
39 Participants
|
|
Microbiological Efficacy Measured by the Number of Participants Achieving Bacteriological Eradication of Gram-positive Baseline Pathogens at the TOC Visit.
Microbiological Failure
|
1 Participants
|
4 Participants
|
Adverse Events
Daptomycin
Pooled Comparator
Serious adverse events
| Measure |
Daptomycin
n=97 participants at risk
Daptomycin 4 mg/kg intravenous (i.v.) once daily
|
Pooled Comparator
n=92 participants at risk
Vancomycin 1 g intravenous (i.v.) twice daily or Teicoplanin 400 mg i.v. once daily following a loading dose of 400 mg administered at 0, 12 and 24 hours on day one.
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/97
|
1.1%
1/92
|
|
Cardiac disorders
Cardiac Arrest
|
0.00%
0/97
|
1.1%
1/92
|
|
Gastrointestinal disorders
Crohn's Disease
|
0.00%
0/97
|
1.1%
1/92
|
|
Gastrointestinal disorders
Inguinal Hernia
|
1.0%
1/97
|
0.00%
0/92
|
|
General disorders
Impaired Healing
|
0.00%
0/97
|
1.1%
1/92
|
|
General disorders
Induration
|
1.0%
1/97
|
0.00%
0/92
|
|
Infections and infestations
Abscess Limb
|
0.00%
0/97
|
1.1%
1/92
|
|
Infections and infestations
Cellulitis
|
1.0%
1/97
|
0.00%
0/92
|
|
Infections and infestations
Erysipelas
|
2.1%
2/97
|
0.00%
0/92
|
|
Infections and infestations
Haemophilus Bacteraemia
|
1.0%
1/97
|
0.00%
0/92
|
|
Infections and infestations
Necrotising Fasciitis
|
0.00%
0/97
|
1.1%
1/92
|
|
Infections and infestations
Pneumonia
|
2.1%
2/97
|
1.1%
1/92
|
|
Infections and infestations
Staphylococcal Skin Infection
|
1.0%
1/97
|
0.00%
0/92
|
|
Injury, poisoning and procedural complications
Open Wound
|
0.00%
0/97
|
1.1%
1/92
|
|
Investigations
Creatinine Renal Clearance Decreased
|
1.0%
1/97
|
0.00%
0/92
|
|
Metabolism and nutrition disorders
Diabetic Foot
|
0.00%
0/97
|
1.1%
1/92
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
1.0%
1/97
|
0.00%
0/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Myeloid Leukaemia
|
0.00%
0/97
|
1.1%
1/92
|
|
Nervous system disorders
Haemorrhage Intracranial
|
0.00%
0/97
|
1.1%
1/92
|
|
Renal and urinary disorders
Renal Failure
|
1.0%
1/97
|
1.1%
1/92
|
|
Renal and urinary disorders
Renal Failure Acute
|
0.00%
0/97
|
1.1%
1/92
|
|
Reproductive system and breast disorders
Acquired Hydrocele
|
1.0%
1/97
|
0.00%
0/92
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
1.0%
1/97
|
0.00%
0/92
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
1.0%
1/97
|
0.00%
0/92
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Oedema
|
1.0%
1/97
|
0.00%
0/92
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
1.0%
1/97
|
0.00%
0/92
|
|
Skin and subcutaneous tissue disorders
Drug Eruption
|
0.00%
0/97
|
2.2%
2/92
|
|
Skin and subcutaneous tissue disorders
Eczema Nummular
|
1.0%
1/97
|
0.00%
0/92
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.0%
1/97
|
0.00%
0/92
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
1.0%
1/97
|
0.00%
0/92
|
|
Skin and subcutaneous tissue disorders
Skin Ulcer
|
1.0%
1/97
|
0.00%
0/92
|
|
Surgical and medical procedures
Skin Graft
|
0.00%
0/97
|
1.1%
1/92
|
|
Vascular disorders
Arterial Occlusive Disease
|
2.1%
2/97
|
0.00%
0/92
|
|
Vascular disorders
Femoral Artery Occlusion
|
0.00%
0/97
|
1.1%
1/92
|
|
Vascular disorders
Hypertension
|
1.0%
1/97
|
0.00%
0/92
|
|
Vascular disorders
Peripheral Ischaemia
|
0.00%
0/97
|
1.1%
1/92
|
|
Vascular disorders
Vasculitis
|
0.00%
0/97
|
1.1%
1/92
|
Other adverse events
| Measure |
Daptomycin
n=97 participants at risk
Daptomycin 4 mg/kg intravenous (i.v.) once daily
|
Pooled Comparator
n=92 participants at risk
Vancomycin 1 g intravenous (i.v.) twice daily or Teicoplanin 400 mg i.v. once daily following a loading dose of 400 mg administered at 0, 12 and 24 hours on day one.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
8.2%
8/97
|
1.1%
1/92
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
6/97
|
4.3%
4/92
|
|
Gastrointestinal disorders
Nausea
|
5.2%
5/97
|
5.4%
5/92
|
|
Investigations
Alanine Aminotransferase Increased
|
2.1%
2/97
|
7.6%
7/92
|
|
Investigations
Aspartate Aminotransferase Increased
|
1.0%
1/97
|
5.4%
5/92
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
1.0%
1/97
|
5.4%
5/92
|
|
Investigations
Blood Lactate Dehydrogenase Increased
|
1.0%
1/97
|
5.4%
5/92
|
|
Investigations
Blood Pressure Increased
|
0.00%
0/97
|
6.5%
6/92
|
|
Investigations
Blood Urea Increased
|
1.0%
1/97
|
7.6%
7/92
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.2%
6/97
|
5.4%
5/92
|
|
Psychiatric disorders
Insomnia
|
5.2%
5/97
|
4.3%
4/92
|
Additional Information
Study Director
Novartis Pharmaceuticals
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.
- Publication restrictions are in place
Restriction type: OTHER