China Registration Study in Patients With Skin Infections

A Phase 3, Multicentre, Randomised, Investigator-blinded, Parallel-groupStudy of the Safety and Efficacy of Intravenous Daptomycin (Cubicin®)Compared With That of Comparator (Vancomycin or Vancomycin Followed by Semi-synthetic Penicillin-cloxacillin) in the Treatment of Chinese Subjects With cSSSI

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00772447

Enrollment

265

Registered

2008-10-15

Start date

2008-09-30

Completion date

2010-09-30

Last updated

2015-03-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Infectious, Skin Diseases

Keywords

Skin Infections, Complicated Bacterial Skin and Skin Structure Infection due to Gram-positive Pathogens

Brief summary

The objectives of this study is to evaluate the Safety and Efficacy of Intravenous Daptomycin (Cubicin®)Compared with that of Comparator (Vancomycin or Vancomycin Followed by Semi-synthetic Penicillin-cloxacillin) in the Treatment of Chinese Subjects with Complicated Bacterial Skin and Skin Structure Infection due to Gram-Positive Pathogens.

Interventions

DRUGVancomycin

Vancomycin - 1g per 12 hrs, for 7-14 days Or switch to Vancomycin Followed by Semi-synthetic Penicillin-Cloxacillin: \- 1 g every 6 hours or 2 g every 8 hours

DRUGDaptomycin

4mg/kg IV ; Q 24 hr (once every 24 hours)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Provision of inform consent * A diagnosis of of complicated skin and skin structure infection known or suspected to be due to Gram-positive bacteria * Diagnosis of bacterial skin and skin structure infection in the presence of some complicating factor, including infections involving deeper soft tissue or requiring surgical intervention, a pre-existing lesion or underlying condition affect healing

Exclusion criteria

* Subjects known to have any bloodstream infection (including bloodstream infection caused by S. aureus). Subjects whose baseline blood cultures are positive for any clinically pathogenic organism ( including S. aureus ) should be discontinued from study * Minor or superficial skin infections, Infected decubitusulcer, Perirectal abscess, Hidradenitis suppurativa, Myositis, Multiple infected ulcers at distant sites, Infected burn wounds of a large area, * Conditions requiring surgery that in and of itself would cure the infection or remove the infected site (eg, amputation) * Conditions requiring emergent surgical intervention at the site of infection (eg, progressive necrotizing infections)

Design outcomes

Primary

Measure	Time frame	Description
Change of Erythrocyte Volume Fraction(Percentage of Erythrocyte Volume in Total Volume of Blood)	baseline to TOC(test of cure), for up to 4 weeks	Erythrocyte volume fraction means under certain conditions, after centrifugation pressing, the percentage of erythrocyte volume in the total volume of blood
Change in Creatinine Clearance	baseline to TOC(test of cure), for up to 4 weeks	—
Change in Serum Total Creatine Phosphokinase (CPK)	baseline to TOC(test of cure), for up to 4 weeks	—
Change in Urine pH	baseline to TOC(test of cure), for up to 4 weeks	—
Shift in ECG	baseline to TOC(test of cure), for up to 4 weeks	percentage of patients who were primarily tested as normal ECG at baseline and changed into abnormal ECG at TOC visit in all the patients with normal ECG at baseline

Secondary

Measure	Time frame	Description
Per-pathogen(Methicillin Sensitive Staphylococcus Aureus) Clinical Response at TOC	baseline and TOC(test of cure), for up to 4 weeks	This is the comparison of clinical efficacy by methicillin sensitive staphylococcus aureus(MSSA) between the two groups. As the analysis was performed by specific pathogen in ME population and clinical efficacy was compared meanwhile, the clinical evaluation was based on the number of cases under the category of specific pathogen rather than the number of strains. Percentage of patients who were cured or improved at TOC visit in the patients who were identified with MSSA infection at baseline of both groups.
Blinded Investigator's Assessement of Clinical Response at TOC(Test of Cure)	baseline and TOC, for up to 4 weeks	The percentage of patients who were cured or clinically improved in the clinical evaluable (CE) population of each arm at TOC visit was analyzed. CE population includes all the patients with no significant deviation from study protocol in full analysis set population, and meetting the following specific criteria: 1.receiving randomly dispensed study treatment at appropriate time(with a compliance of at least 80% or 4 days \[3 days for patients evaluated as treatment failure\]). 2.without the administration of potentially confounding non-investigational antibiotics (using one potentially effective non-investigational antibiotic for the treatment of primary infection due to other reasons than lack of efficacy from Day 1 to TOC \[for systemicadministration of non-glycopeptides, \>1 calendar day\]). 3.meeting the study inclusion/exclusion criteria 4.necessary clinical evaluation performed (evaluation for effectiveness at TOC visit, except for the condition confirmed as clinically ineffective)
Per-pathogen(Staphylococcus Aureus) Microbiological Response at TOC	baseline and TOC(test of cure), for up to 4 weeks	This is the comparison of clinical efficacy by staphylococcus aureus between the two groups. As the analysis was performed by specific pathogen in ME population and clinical efficacy was compared meanwhile, the clinical evaluation was based on the number of cases under the category of specific pathogen rather than the number of strains. Percentage of patients who were cured or improved at TOC visit in the patients who were identified with staphylococcus aureus infection at baseline of both groups.
Blinded Investigator's Assessement of Clinical Response at EOT(End of Therapy)	baseline and EOT(end of therapy), for up to 2 weeks	The percentage of patients who were cured or clinically improved in the clinical evaluable (CE) population at EOT visit was analyzed. CE population includes all the patients with no significant deviation from study protocol in full analysis set population, and meetting the following specific criteria: 1.receiving randomly dispensed study treatment at appropriate time(with a compliance of at least 80% or 4 days \[3 days for patients evaluated as treatment failure\]). 2.without the administration of potentially confounding non-investigational antibiotics (using one potentially effective non-investigational antibiotic for the treatment of primary infection due to other reasons than lack of efficacy from Day 1 to TOC \[for systemicadministration of non-glycopeptides, \>1 calendar day\]). 3.meeting the study inclusion/exclusion criteria 4.necessary clinical evaluation performed (evaluation for effectiveness at TOC visit, except for the condition confirmed as clinically ineffective)
Microbiological Response at TOC(Test of Cure)	baseline and TOC, for up to 4 weeks	The microbiological response rate (removal or presumed removal) in ME(microbiological evaluable) population of daptomycin group and comparator group at TOC visit was analyzed. ME population includes all the patients with Gram-positive pathogenic bacteria isolated at baseline in CE population. Microbiological response rate means the percentage of strains which were removed or presumably removed at TOC visit in all the strains isolated from ME population at baseline.
Microbiological Response at EOT(End of Therapy)	baseline and EOT, for up to 2 weeks	The microbiological response rate (removal or presumed removal) in ME(microbiological evaluable) population of daptomycin group and comparator group at EOT visit was analyzed. ME population includes all the patients with Gram-positive pathogenic bacteria isolated at baseline in CE population. Microbiological response rate means the percentage of strains which were removed or presumably removed at EOT visit in all the strains isolated from ME population at baseline.
Per-pathogen(Methicillin Resistant Staphylococcus Aureus) Clinical Response at TOC(Test of Cure)	baseline and TOC, for up to 4 weeks	This is the comparison of clinical efficacy by methicillin resistant staphylococcus aureus(MRSA) between the two groups. As the analysis was performed by specific pathogen in ME population and clinical efficacy was compared meanwhile, the clinical evaluation was based on the number of cases under the category of specific pathogen rather than the number of strains. Percentage of patients who were cured or improved at TOC visit in the patients who were identified with MRSA infection at baseline of both groups.

Countries

China

Participant flow

Recruitment details

Overall, 265 patients were randomised (daptomycin: 131 patients, comparator: 134 patients), with 264 patients receiving study treatment

Participants by arm

Arm	Count
Daptomycin daptomycin 4mg/kg iv every 24hours	130
Vancomycin, or Vancomycin Switch to Cloxacillin vancomycin 1g per 12 hours, for 7-14 days; or switch to cloxacillin: 1 g every 6 hours or 2 g every 8 hours	134
Total	264

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	all others	2	2
Overall Study	incorrect enrolment	3	4
Overall Study	Lost to Follow-up	2	4
Overall Study	Physician Decision	4	8
Overall Study	Protocol Violation	0	1
Overall Study	Withdrawal by Subject	9	5

Baseline characteristics

Characteristic	Daptomycin	Vancomycin, or Vancomycin Switch to Cloxacillin	Total
Age, Continuous	44.2 years STANDARD_DEVIATION 15.77	44.5 years STANDARD_DEVIATION 16.02	44.3 years STANDARD_DEVIATION 15.87
Sex: Female, Male Female	90 Participants	95 Participants	185 Participants
Sex: Female, Male Male	40 Participants	39 Participants	79 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	30 / —	39 / —
serious Total, serious adverse events	1 / —	3 / —