Trial Outcomes & Findings for Daptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA (NCT NCT01419184)

NCT ID: NCT01419184

Last Updated: 2018-09-05

Results Overview

Infection Related Hospital Length of Stay (IRLOS) is defined as the number of hours of hospitalization associated with antibiotic treatment of the complicated skin and skin structure infections (cSSSI) beginning at initiation of study-antibiotic administration and ending at discontinuation of all antibiotic therapy for cSSSI or at hospital discharge (whichever occurred first). This included continued hospitalization for treatment of adverse events resulting from use of the study antibiotic or subsequent antimicrobial therapy. The mean number of hours for each treatment group is presented.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

250 participants

Primary outcome timeframe

Baseline (Day 0) through the End of Hospital Stay (up to Day 14)

Results posted on

2018-09-05

Participant Flow

One participant enrolled in the study but was lost to follow up prior to being randomized to either treatment arm (daptomycin or vancomycin). This participant did not receive study drug and was not included in further analysis. No further details are available for this participant.

Participant milestones

Participant milestones
Measure	Daptomycin Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for complicated skin and skin structure infections (cSSSI) or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin Vancomycin was reconstituted per the manufacturer's instructions and was dosed per investigator's discretion and was administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occured first. Investigators treated participants according to their usual decision-making and discretion.
Overall Study STARTED	128	121
Overall Study Received at Least 1 Dose of Study Drug	118	106
Overall Study COMPLETED	118	106
Overall Study NOT COMPLETED	10	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Daptomycin Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for complicated skin and skin structure infections (cSSSI) or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin Vancomycin was reconstituted per the manufacturer's instructions and was dosed per investigator's discretion and was administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occured first. Investigators treated participants according to their usual decision-making and discretion.
Overall Study Site data not available	3	2
Overall Study No IRLOS-No in-patient end date reported	3	6
Overall Study No IRLOS-randomized, not treated	2	4
Overall Study No IRLOS-non trial antibiotic used	1	2
Overall Study No IRLOS-No adverse event treatment date	0	1
Overall Study Participant randomized, not treated	1	0

Baseline Characteristics

Daptomycin Versus Vancomycin in Participants With Skin Infections Due to MRSA

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daptomycin n=118 Participants Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin n=106 Participants Vancomycin was reconstituted per the manufacturer's instructions and was dosed and administered intravenously until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Total n=224 Participants Total of all reporting groups
Age, Customized 18-29 Years Old	16 participants n=5 Participants	10 participants n=7 Participants	26 participants n=5 Participants
Age, Customized 30-39 Years Old	22 participants n=5 Participants	17 participants n=7 Participants	39 participants n=5 Participants
Age, Customized 40-49 Years Old	30 participants n=5 Participants	21 participants n=7 Participants	51 participants n=5 Participants
Age, Customized 50-59 Years Old	26 participants n=5 Participants	32 participants n=7 Participants	58 participants n=5 Participants
Age, Customized 60-69 Years Old	14 participants n=5 Participants	21 participants n=7 Participants	35 participants n=5 Participants
Age, Customized 70+ Years Old	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	49 Participants n=7 Participants	103 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	57 Participants n=7 Participants	121 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) through the End of Hospital Stay (up to Day 14)

Population: The primary analytic sample (subset of the entire sample) comprised participants receiving at least 1 dose of study drug with complete data to calculate the primary outcome, IRLOS. As the end of the IRLOS depended upon the participant's course of treatment, no static set of items were answered to determine if a participant had complete data.

Outcome measures

Outcome measures
Measure	Daptomycin n=118 Participants Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin n=106 Participants Vancomycin was reconstituted per the manufacturer's instructions and was dosed and administered intravenously until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Infection-Related Hospital Length of Stay	91.46 Hours Standard Deviation 57.81	93.23 Hours Standard Deviation 60.78

SECONDARY outcome

Timeframe: Baseline (Day 0), End of Hospital Stay (up to Day 14)

Population: The primary analytic sample (subset of the entire sample) comprised participants receiving at least 1 dose of study drug with complete data to calculate the primary outcome, IRLOS. Participants also had evaluable BPI-SF data at baseline and at hospital discharge.

Pain was measured as the amount of pain experienced "right now" by the participant using an 11-point numerical rating scale adapted from Brief Pain Inventory-Short Form (BPI-SF). Participants were asked to rate pain in his or her skin infection from 0 to 10, where 0 is no pain and 10 is pain as bad as he or she could imagine. Change from baseline to hospital discharge is presented; a negative value represents a decrease in pain.

Outcome measures

Outcome measures
Measure	Daptomycin n=105 Participants Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin n=98 Participants Vancomycin was reconstituted per the manufacturer's instructions and was dosed and administered intravenously until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Mean Change From Baseline to Hospital Discharge in Pain According to the Brief Pain Inventory-Short Form (BPI-SF)	-2.08 units on a scale Standard Deviation 3.13	-2.54 units on a scale Standard Deviation 3.46

SECONDARY outcome

Timeframe: Baseline (Day 0), End of Hospital Stay (up to Day 14)

Population: The primary analytic sample (subset of the entire sample) comprised participants receiving at least 1 dose of study drug with complete data to calculate the primary outcome, IRLOS. Participants also had evaluable EQ-5D data at baseline and at hospital discharge.

Health-related quality of life (HRQoL) was measured using the EuroQol-5 Dimensions, 5 Level (EQ-5D-5L) multi-attribute questionnaire. The 5 dimensions measured were: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant's health state was expressed by a descriptive profile of a 5 digit number. The EQ-5D health states were converted into a single summary index (from 0 to 1, with 0 representing death, to 1 representing perfect health) by applying weights to each of the levels in each dimension. Change from baseline to hospital discharge is presented; positive values represent an increase in health utility.

Outcome measures

Outcome measures
Measure	Daptomycin n=105 Participants Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin n=98 Participants Vancomycin was reconstituted per the manufacturer's instructions and was dosed and administered intravenously until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Mean Change From Baseline to Hospital Discharge in Participant-reported Health-related Quality of Life (HRQoL)	0.12 units on a scale Standard Deviation 0.20	0.18 units on a scale Standard Deviation 0.21

SECONDARY outcome

Timeframe: End of Hospital Stay (up to Day 14)

Population: The primary analytic sample (subset of the entire sample) comprised participants receiving at least 1 dose of study drug with complete data to calculate the primary outcome, IRLOS. Participants also had evaluable PGI-I data at hospital discharge.

PGI-I assessments of improvement were measured by asking participants: How is your skin infection today compared to how it was yesterday? Scores were calculated based on response to the single item, where 1 = improved a lot; 2 = improved moderately; 3 = improved a little; 4 = no change; 5 = worsened a little; 6 = worsened moderately; 7 = worsened a lot. Mean PGI-I scores are presented at hospital discharge; lower values represent greater improvement.

Outcome measures

Outcome measures
Measure	Daptomycin n=102 Participants Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin n=97 Participants Vancomycin was reconstituted per the manufacturer's instructions and was dosed and administered intravenously until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Participant Global Impression of Improvement (PGI-I) at Hospital Discharge	2.05 units on a scale Standard Deviation 1.16	1.80 units on a scale Standard Deviation 0.94

SECONDARY outcome

Timeframe: End of Hospital Stay (up to Day 14) through 30 days post hospital discharge

Population: The primary analytic sample (subset of the entire sample) comprised participants receiving at least 1 dose of study drug with complete data to calculate the primary outcome, IRLOS.

Hospital readmission rates were defined as readmission to an inpatient hospital facility within 30 days of hospital discharge for management of cSSSI relapse or treatment of adverse events related to cSSSI treatment. It did not include all-cause readmissions (for completeness, all-cause readmissions are reported in the descriptive tables). Participants were asked if they had been readmitted to the hospital since their discharge and whether the admission was specifically for their skin infection. The number of participants who were re-hospitalized for skin infection or side effects due to skin infection medication within 30 days since the initial hospital discharge (Day 14) is presented.

Outcome measures

Outcome measures
Measure	Daptomycin n=118 Participants Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin n=106 Participants Vancomycin was reconstituted per the manufacturer's instructions and was dosed and administered intravenously until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
30-day cSSSI-related Hospital Readmission Rates	5 participants	2 participants

SECONDARY outcome

Timeframe: Baseline (Day 0) through 30 days post hospital discharge

Population: The primary analytic sample (subset of the entire sample) comprised participants receiving at least 1 dose of study drug with complete data to calculate the primary outcome, IRLOS.

Direct medical costs were based on utilization of health resources. Unit cost data were obtained from sources external to the trial and assigned to corresponding medical resource utilization observed within the trial to estimate costs of care. cSSSI-related costs were reported from a societal perspective, and further broken down into a health care system perspective. The health care system perspective includes hospital and outpatient costs. The societal perspective includes the health care system perspective plus participant and caregiver time loss from work and participant and caregiver out-of-pocket expenses. Total cost (including both total inpatient and total post-discharge costs) per participant is presented.

Outcome measures

Outcome measures
Measure	Daptomycin n=118 Participants Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin n=106 Participants Vancomycin was reconstituted per the manufacturer's instructions and was dosed and administered intravenously until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
cSSSI-related Medical Resource Utilization and Costs Health Care System Perspective	10441.30 dollars (United States) Standard Deviation 7952.40	9894.34 dollars (United States) Standard Deviation 6620.51
cSSSI-related Medical Resource Utilization and Costs Societal Perspective	11085.57 dollars (United States) Standard Deviation 8120.20	10397.24 dollars (United States) Standard Deviation 6827.55

Adverse Events

Daptomycin

Serious events: 15 serious events

Other events: 0 other events

Deaths: 0 deaths

Vancomycin

Serious events: 9 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Vice President, Clinical Research

Cubist Pharmaceuticals

Phone: 1.781.860.8660

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Daptomycin n=118 participants at risk Daptomycin 4 milligrams per kilogram (mg/kg) was administered intravenously once a day until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.	Vancomycin n=106 participants at risk Vancomycin was reconstituted per the manufacturer's instructions and was dosed and administered intravenously until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Blood and lymphatic system disorders Atrial Fibrillation	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Cardiac disorders cardiac arrest	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Cardiac disorders Sinus bradycardia	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
General disorders Lyme infection, Lyme disease	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Immune system disorders Allergic reaction (dermatologic)	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Infections and infestations Osteomyelitis, Foot	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Infections and infestations Worsening infection to left hand due to non-compliance	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Infections and infestations Right prepatella bursitis with abscess, Bursitis infective	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Infections and infestations Acute Viral Syndrome	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Infections and infestations Bilat Lower Extrem Cellulitis, Cellulitis of legs	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Infections and infestations Chest Wall infection status post right breast implant removal	1.9% 1/54 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/49 Only serious adverse events were collected for this study.
Infections and infestations Clinical worsening of right below knee stump infection	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Infections and infestations Left hallux osteomyelitis	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Infections and infestations Osteomyelitis	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Infections and infestations Osteomyelitis with septic arthritis	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Infections and infestations Pneumonia	1.7% 2/118 • Number of events 2 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Infections and infestations Right Leg Cellulitis	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Nervous system disorders Seizure	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Psychiatric disorders altered mental status	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Renal and urinary disorders respiratory failure	0.00% 0/118 Only serious adverse events were collected for this study.	0.94% 1/106 • Number of events 1 Only serious adverse events were collected for this study.
Renal and urinary disorders Renal insufficiency	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Skin and subcutaneous tissue disorders red man syndrome	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.
Social circumstances social admission for reassignment of nursing home	0.85% 1/118 • Number of events 1 Only serious adverse events were collected for this study.	0.00% 0/106 Only serious adverse events were collected for this study.