Trial Outcomes & Findings for Evaluation of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections (NCT NCT01499277)

Last Updated: 2017-09-06

Results Overview

The observed difference in the clinical cure rates at TOC (ceftaroline group minus vancomycin plus aztreonam group) in MITT. Clinical cure rate is measured by comparing the participant's signs and symptoms at TOC visit to those recorded at study baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

802 participants

Primary outcome timeframe

7 to 20 days after the last dose of study drug

Results posted on

2017-09-06

Participant Flow

Overall, 802 patients were enrolled from 111 centres in 6 regions in this study. The first patient was enrolled on 17 May 2012 and the last patient last visit was on 26 June 2014. Of 802 enrolled participants, 30 did not meet the eligibility criteria and 11 were randomized but not treated.

Participant milestones

Participant milestones
Measure	Ceftaroline Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam Vancomycin Plus Aztreonam
Overall Study STARTED	506	255
Overall Study COMPLETED	459	223
Overall Study NOT COMPLETED	47	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Ceftaroline Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam Vancomycin Plus Aztreonam
Overall Study Adverse Event	3	6
Overall Study Death	3	2
Overall Study Lost to Follow-up	15	8
Overall Study Protocol Violation	2	3
Overall Study Withdrawal by Subject	16	6
Overall Study Lack of therapeutic response and other	8	7

Baseline Characteristics

Evaluation of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ceftaroline n=506 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=255 Participants Vancomycin Plus Aztreonam	Total n=761 Participants Total of all reporting groups
Age, Continuous	52.6 Years STANDARD_DEVIATION 16.51 • n=5 Participants	53.6 Years STANDARD_DEVIATION 16.25 • n=7 Participants	52.9 Years STANDARD_DEVIATION 16.42 • n=5 Participants
Sex: Female, Male Female	196 Participants n=5 Participants	107 Participants n=7 Participants	303 Participants n=5 Participants
Sex: Female, Male Male	310 Participants n=5 Participants	148 Participants n=7 Participants	458 Participants n=5 Participants

PRIMARY outcome

Timeframe: 7 to 20 days after the last dose of study drug

Population: Modified intent-to-treat (MITT)

Outcome measures

Outcome measures
Measure	Ceftaroline n=506 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=255 Participants Vancomycin Plus Aztreonam
Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set Clinical cure	396 Participant Interval -6.9 to 5.41	202 Participant
Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set Clinical failure	58 Participant	34 Participant
Clinical Response at Test of Cure (TOC) in Modified Intent-to-treat (MITT) Analysis Set indeterminate	52 Participant	19 Participant

PRIMARY outcome

Timeframe: 7 to 20 days after the last dose of study drug

Population: Clinical evaluable (CE)

The observed difference in the clinical cure rates at TOC (ceftaroline group minus vancomycin plus aztreonam group) in CE. Clinical cure rate is measured by comparing the participant's signs and symptoms at TOC visit to those recorded at study baseline.

Outcome measures

Outcome measures
Measure	Ceftaroline n=395 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=211 Participants Vancomycin Plus Aztreonam
Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set Clinical cure	342 Participant	180 Participant
Clinical Response at TOC in Clinically Evaluable (CE) Analysis Set Clinical failure	53 Participant	31 Participant

SECONDARY outcome

Timeframe: 7 to 20 days after the last dose of study drug

Population: Microbiologically modified-intent-to-treat (mMITT)

Difference in microbiological favorable response rate at TOC in mMITT analysis set. Favorable microbiological response rate is measured by comparing TOC microbiological data to baseline microbiological data. In the absence of TOC microbiological data it is presumed from the clinical response.

Outcome measures

Outcome measures
Measure	Ceftaroline n=248 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=136 Participants Vancomycin Plus Aztreonam
Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set Unfavorable	17 Participant	17 Participant
Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set Indeterminate	28 Participant	10 Participant
Per Patient Microbiological Response at TOC in Microbiologically Modified-intent-to-treat (mMITT) Analysis Set Favorable	203 Participant	109 Participant

SECONDARY outcome

Timeframe: 7 to 20 days after the last dose of study drug

Population: Microbiologically evaluable (ME)

Difference in microbiological favorable response rate at TOC in ME. Favourable microbiological response rate is measured by comparing TOC microbiological data to baseline microbiological data. In the absence of TOC microbiological data it is presumed from the clinical response.

Outcome measures

Outcome measures
Measure	Ceftaroline n=181 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=112 Participants Vancomycin Plus Aztreonam
Per-patient Micro Response at TOC in Microbiologically Evaluable (ME) Analysis Set Favourable	167 Participant	98 Participant
Per-patient Micro Response at TOC in Microbiologically Evaluable (ME) Analysis Set Unfavorable	14 Participant	14 Participant

SECONDARY outcome

Timeframe: On day of last dose of study drug (or + 1 day)

The observed difference in the clinical cure rates at EOT (ceftaroline group minus vancomycin plus aztreonam group) in MITT. Clinical cure rate is measured by comparing the participant's signs and symptoms at EOT visit to those recorded at study baseline.

Outcome measures

Outcome measures
Measure	Ceftaroline n=506 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=255 Participants Vancomycin Plus Aztreonam
Clinical Response at End of Treatment (EOT) in MITT Analysis Set Clinical cure	429 Participants	213 Participants
Clinical Response at End of Treatment (EOT) in MITT Analysis Set Clinical failure	44 Participants	29 Participants
Clinical Response at End of Treatment (EOT) in MITT Analysis Set Indeterminate	31 Participants	11 Participants
Clinical Response at End of Treatment (EOT) in MITT Analysis Set Missing	2 Participants	2 Participants

SECONDARY outcome

Timeframe: On day of last dose of study drug (or +1 day)

The observed difference in the clinical cure rates at EOT (ceftaroline group minus vancomycin plus aztreonam group) in CE. Clinical cure rate is measured by comparing the participant's signs and symptoms at EOT visit to those recorded at study baseline.

Outcome measures

Outcome measures
Measure	Ceftaroline n=395 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=211 Participants Vancomycin Plus Aztreonam
Clinical Response at EOT in CE Analysis Set Clinical cure	356 Participants	184 Participants
Clinical Response at EOT in CE Analysis Set Clinical failure	39 Participants	27 Participants

SECONDARY outcome

Timeframe: 21 to 42 days after the last dose of study drug

The observed difference in the clinical relapse rates at LFU (ceftaroline group minus vancomycin plus aztreonam group) in CE. Clinical relapse rate at LFU is measured by comparing a patient's signs and symptoms at late follow-up to those when they were cured at TOC.

Outcome measures

Outcome measures
Measure	Ceftaroline n=342 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=180 Participants Vancomycin Plus Aztreonam
Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC Relapse	3 Participants	3 Participants
Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC No relapse	335 Participants	174 Participants
Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC Indeterminate	3 Participants	3 Participants
Clinical Relapse at Late Follow-up (LFU) in CE Patients Who Were Cured at TOC Missing	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 48 to 72 hours after first dose of study drug

The observed difference in the early success rates at 48 to 72 hours of treatment (ceftaroline group minus vancomycin plus aztreonam group) in MITT. Early response rate as measured by comparing the participant's signs and symptoms at the 48-72 hour visit to those recorded at study baseline.

Outcome measures

Outcome measures
Measure	Ceftaroline n=506 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=255 Participants Vancomycin Plus Aztreonam
Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set success	445 Participants	229 Participants
Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set failure	28 Participants	11 Participants
Early Response at 48 to 72 Hours of Treatment in MITT Analysis Set Indeterminate	33 Participants	15 Participants

SECONDARY outcome

Timeframe: 7 to 20 days after the last dose of study drug

Per-pathogen microbiological response at TOC by baseline pathogen from site of skin infection in ME analysis set

Outcome measures

Outcome measures
Measure	Ceftaroline n=181 Participants Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=112 Participants Vancomycin Plus Aztreonam
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Enterococcus faecalis - Unfavorable; (n=6, 5)	1 Participants	1 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Escherichia coli - Favorable; (n=12, 10)	12 Participants	9 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Escherichia coli - Unfavorable; (n=12, 10)	0 Participants	1 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Klebsiella pneumoniae - Favorable; (n=7, 4)	6 Participants	3 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Klebsiella pneumoniae - Unfavorable; (n=7, 4)	1 Participants	1 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Klebsiella oxytoca - Favorable; (n=4, 1)	4 Participants	1 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Klebsiella oxytoca - Unfavorable; (n=4, 1)	0 Participants	0 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Proteus mirabilis - Favorable; (n=7, 2)	6 Participants	2 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Proteus mirabilis - Unfavorable; (n=7, 2)	1 Participants	0 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Morganella morganii - Favorable; (n=4, 2)	4 Participants	2 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Morganella morganii - Unfavorable; (n=4, 2)	0 Participants	0 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Enterobacter cloacae - Favorable; (n=4, 5)	4 Participants	5 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Enterobacter cloacae - Unfavorable; (n=4, 5)	0 Participants	0 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME MSSA - Favorable; (n=94, 57)	91 Participants	49 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME MSSA - Unfavorable; (n=94, 57)	3 Participants	8 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME MRSA - Favorable; (n=25, 15)	22 Participants	12 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME MRSA - Unfavorable; (n=25, 15)	3 Participants	3 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Streptococcus pyogenes - Favorable; (n=15, 7)	14 Participants	7 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Streptococcus pyogenes - Unfavorable; (n=15, 7)	1 Participants	0 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Streptococcus agalactiae - Favorable; (n=6, 9)	6 Participants	9 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Streptococcus agalactiae - Unfavorable; (n=6, 9)	0 Participants	0 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Streptococcus dysgalactiae - Favorable; (n=9, 0)	9 Participants	0 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Streptococcus dysgalactiae - Unfavorable; (n=9, 0)	0 Participants	0 Participants
Per-pathogen Microbiological Response at TOC by Baseline Pathogen From Site of Skin Infection in ME Enterococcus faecalis - Favorable; (n=6, 5)	5 Participants	4 Participants

Adverse Events

Ceftaroline

Serious events: 31 serious events

Other events: 82 other events

Deaths: 0 deaths

Vancomycin/Aztreonam

Serious events: 15 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ceftaroline n=506 participants at risk Ceftaroline fosamil at 600 mg every 8 hours (q8h)	Vancomycin/Aztreonam n=255 participants at risk Vancomycin Plus Aztreonam
Blood and lymphatic system disorders Anaemia	2.0% 10/506 • Number of events 10 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).	3.5% 9/255 • Number of events 9 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Gastrointestinal disorders Constipation	1.8% 9/506 • Number of events 9 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).	3.1% 8/255 • Number of events 8 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Gastrointestinal disorders Diarrhoea	2.4% 12/506 • Number of events 12 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).	2.0% 5/255 • Number of events 5 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Gastrointestinal disorders Nausea	4.0% 20/506 • Number of events 20 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).	4.3% 11/255 • Number of events 11 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Gastrointestinal disorders Vomiting	2.6% 13/506 • Number of events 15 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).	2.0% 5/255 • Number of events 5 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Metabolism and nutrition disorders Hypokalaemia	2.8% 14/506 • Number of events 14 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).	3.1% 8/255 • Number of events 9 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Nervous system disorders Headache	3.4% 17/506 • Number of events 17 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).	4.7% 12/255 • Number of events 13 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Skin and subcutaneous tissue disorders Rash	2.0% 10/506 • Number of events 11 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).	2.4% 6/255 • Number of events 6 • Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).

Additional Information

Yunxia Lu

AstraZeneca-PPD

Phone: 910-558-4197

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees not to use such Confidential study information and not to disclose them to any other third parties, except that the undersigned shall not be prevented from using or disclosing information: (a) which by written records was previously known; (b) which is now public knowledge, (c) which is lawfully obtained by the undersigned from sources who have a lawful right to disclose such information.
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