Trial Outcomes & Findings for Comparative Study of Ceftaroline vs. Vancomycin Plus Aztreonam in Adult Subjects With Complicated Skin Infections (NCT NCT00423657)

Last Updated: 2017-03-14

Results Overview

Cure: Total resolution of all signs and symptoms of the baseline infection, or improvement of the infection such that no further antimicrobial therapy was necessary. Failure: Requirement of alternative antimicrobial therapy for primary infection of complicated skin and skin structure infection (cSSSI) due to inadequate response, recurrence, new infection at the same site; treatment-limiting adverse event (AE); requirement for surgery due to failure of study drug; diagnosis of osteomyelitis after Study Day 8; or death caused by cSSSI. Indeterminate: Inability to determine an outcome

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

680 participants

Primary outcome timeframe

8-15 days after last dose of study drug administration

Results posted on

2017-03-14

Participant Flow

Patients were recruited worldwide from March 2007 to December 2007

Patients were screened for up to 24 hours

Participant milestones

Participant milestones
Measure	Ceftaroline for Injection Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.	IV Vancomycin Plus IV Aztreonam Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours.
Overall Study STARTED	342	338
Overall Study COMPLETED	316	313
Overall Study NOT COMPLETED	26	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Ceftaroline for Injection Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.	IV Vancomycin Plus IV Aztreonam Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours.
Overall Study Request of sponsor/investigator	1	0
Overall Study Withdrew consent	10	8
Overall Study Non-compliance	0	1
Overall Study Other	15	16

Baseline Characteristics

Comparative Study of Ceftaroline vs. Vancomycin Plus Aztreonam in Adult Subjects With Complicated Skin Infections

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ceftaroline for Injection n=342 Participants Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.	IV Vancomycin Plus IV Aztreonam n=338 Participants Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours.	Total n=680 Participants Total of all reporting groups
Age, Customized <=18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Customized >18 and < 65 years	281 participants n=5 Participants	291 participants n=7 Participants	572 participants n=5 Participants
Age, Customized >=65 years	61 participants n=5 Participants	47 participants n=7 Participants	108 participants n=5 Participants
Age, Continuous	47.8 years STANDARD_DEVIATION 16.98 • n=5 Participants	47.5 years STANDARD_DEVIATION 16.07 • n=7 Participants	47.7 years STANDARD_DEVIATION 16.52 • n=5 Participants
Sex: Female, Male Female	118 Participants n=5 Participants	137 Participants n=7 Participants	255 Participants n=5 Participants
Sex: Female, Male Male	224 Participants n=5 Participants	201 Participants n=7 Participants	425 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	63 Participants n=5 Participants	59 Participants n=7 Participants	122 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	279 Participants n=5 Participants	279 Participants n=7 Participants	558 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8-15 days after last dose of study drug administration

Population: MITT (Modified Intent to Treat) - all subjects that received any amount of study drug

Outcome measures

Outcome measures
Measure	Ceftaroline for Injection n=342 Participants Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.	IV Vancomycin Plus IV Aztreonam n=338 Participants Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours.
Clinical Cure Rate at Test of Cure (TOC) (MITT Population) Clinical Cure	291 participants	289 participants
Clinical Cure Rate at Test of Cure (TOC) (MITT Population) Clinical Failure	25 participants	28 participants
Clinical Cure Rate at Test of Cure (TOC) (MITT Population) Indeterminate	26 participants	21 participants

Serious events: 14 serious events

Other events: 144 other events

Deaths: 0 deaths

IV Vancomycin Plus IV Aztreonam

Serious events: 16 serious events

Other events: 159 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Vice President, Clinical Sciences

Cerexa, Inc.

Phone: (510) 285-9200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ceftaroline for Injection n=341 participants at risk Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.	IV Vancomycin Plus IV Aztreonam n=339 participants at risk Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours.
Blood and lymphatic system disorders Anemia	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Cardiac disorders Bradycardia	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Cardiac disorders Myocardial infarction	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Cardiac disorders Sinoatrial block	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Gastrointestinal disorders Abdominal pain	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Gastrointestinal disorders Ileus	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
General disorders Multi-organ failure	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
General disorders Condition aggravated	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Hepatobiliary disorders Hepatitis	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Immune system disorders Anaphylactic shock	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Immune system disorders Anaphylactoid reaction	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Infections and infestations Bacteremia	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Infections and infestations Central line infection	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Infections and infestations Wound infection	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Infections and infestations Osteomyelitis	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Infections and infestations Pneumonia	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Infections and infestations Sepsis	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Injury, poisoning and procedural complications Accidental overdose	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Injury, poisoning and procedural complications Dislocation of joint prosthesis	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Injury, poisoning and procedural complications Postprocedural hemorrhage	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukemia recurrent	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Nervous system disorders Convulsion	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Nervous system disorders Loss of consciousness	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Renal and urinary disorders Acute prerenal failure	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Renal and urinary disorders Renal failure	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Renal and urinary disorders Renal failure acute	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Respiratory, thoracic and mediastinal disorders Acute pulmonary edema	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Vascular disorders Hypotension	0.29% 1/341 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.00% 0/339 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Vascular disorders Thrombophlebitis	0.00% 0/341 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.29% 1/339 • Number of events 1 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.

Measure	Ceftaroline for Injection n=341 participants at risk Ceftaroline fosamil 600 mg administered intravenously over 60 minutes every 12 hours, followed by placebo administered over 60 minutes every 12 hours.	IV Vancomycin Plus IV Aztreonam n=339 participants at risk Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours.
Gastrointestinal disorders Diarrhea	6.5% 22/341 • Number of events 22 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	4.4% 15/339 • Number of events 15 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Gastrointestinal disorders Nausea	6.2% 21/341 • Number of events 21 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	5.6% 19/339 • Number of events 19 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Nervous system disorders Headache	5.3% 18/341 • Number of events 18 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	5.3% 18/339 • Number of events 18 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Skin and subcutaneous tissue disorders Pruritus	3.8% 13/341 • Number of events 13 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	8.3% 28/339 • Number of events 28 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Psychiatric disorders Insomnia	3.5% 12/341 • Number of events 12 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	2.4% 8/339 • Number of events 8 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Skin and subcutaneous tissue disorders Rash	3.2% 11/341 • Number of events 11 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	2.9% 10/339 • Number of events 10 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Gastrointestinal disorders Vomiting	3.2% 11/341 • Number of events 11 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	2.7% 9/339 • Number of events 9 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Gastrointestinal disorders Constipation	2.9% 10/341 • Number of events 10 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	3.2% 11/339 • Number of events 11 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Vascular disorders Hypertension	2.3% 8/341 • Number of events 8 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	0.88% 3/339 • Number of events 3 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Investigations Blood pressure increased	2.1% 7/341 • Number of events 7 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	1.2% 4/339 • Number of events 4 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Metabolism and nutrition disorders Hypokalemia	1.5% 5/341 • Number of events 5 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	2.7% 9/339 • Number of events 9 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Investigations Alanine aminotransferase increase	1.5% 5/341 • Number of events 5 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	2.1% 7/339 • Number of events 7 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
General disorders Pyrexia	1.5% 5/341 • Number of events 5 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	2.1% 7/339 • Number of events 7 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Blood and lymphatic system disorders Anemia	1.2% 4/341 • Number of events 4 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	2.4% 8/339 • Number of events 8 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.
Skin and subcutaneous tissue disorders Erythema	0.59% 2/341 • Number of events 2 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.	2.4% 8/339 • Number of events 8 All safety analyses were performed on the Safety Population which consists of all subjects who received any amount of actual study drug.