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

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00424190
• Collaborator: (none)
• Enrollment: 698
• Locations: 52
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 13.4
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of complicated skin infections in adults.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Infections	Drug: IV Vancomycin plus IV Aztreonam; Drug: Ceftaroline	Phase 3

Detailed Description

Additional purpose of the study is to compare ceftaroline effectivity versus Vancomycin plus Aztreonam in the treatment of complicated skin infections in adults.

Study Design

• Study Type: Interventional
• Actual Enrollment: 698 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Comparative Study to Evaluate the Safety and Efficacy of Ceftaroline Versus Vancomycin Plus Aztreonam in Adult Subjects With Complicated Skin and Skin Structure Infection
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ceftaroline for Injection	Drug: Ceftaroline; 600 mg parenteral infused over 60 minutes, every 12 hours for 5 to 14 days; Other Names: Experimental
Active Comparator: IV Vancomycin and IV Aztreonam	Drug: IV Vancomycin plus IV Aztreonam; vancomycin at 1 g parenteral infused over 60 minutes followed by aztreonam 1 g infused over 60 minutes, every 12 hours, for 5 to 14 days.; Other Names: Active Comparator

Outcome Measures

Primary Outcome Measures

1. Clinical Cure Rate at Test of Cure (TOC) (MITT Population) [8-15 days after the end of treatment]

   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 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

2. Clinical Cure Rate of Ceftaroline Compared With That of Vancomycin Plus Aztreonam Treatment at TOC in the Clinically Evaluable (CE) Population [8-15 days after last dose of study drug]

Secondary Outcome Measures

1. Microbiological Success Rate at the TOC Visit [8-15 days after last dose of study drug]

2. Clinical Response at the End of Therapy (EOT) Visit [Last day of study drug administration]

3. Clinical and Microbiological Response by Pathogen at the TOC Visit [8-15 days after last dose of study drug]

4. Clinical Relapse at the Late Follow Up (LFU) Visit [21 to 35 days after the last dose of study drug]

5. Microbiological Reinfection or Recurrence at the LFU Visit [21 to 35 days after the last dose of study drug]

6. Assess Safety [First dose of study drug through TOC visit]

   Comparisons of the number of participants with Adverse Events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Skin and skin structure infection (SSSI) that involves deeper soft tissue or requires significant surgical intervention, or cellulitis or abscess on lower extremity which occurs in subjects with diabetes mellitus or well-documented peripheral vascular disease.

Exclusion Criteria:

• Prior treatment of current cSSSI with an antimicrobial.

• Failure of vancomycin or aztreonam as therapy for the current cSSSI, or prior isolation of an organism with in vitro resistance to vancomycin or aztreonam.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site	Dothan	Alabama	United States	36301
2	Investigational Site	Long Beach	California	United States	90813
3	Investigational Site	Los Angeles	California	United States	90015
4	Investigational Site	Sacramento	California	United States	95817
5	Investigational Site	Sacramento	California	United States	95819
6	Investigational Site	San Diego	California	United States	92114
7	Investigational Site	San Francisco	California	United States	94110
8	Investigational Site	Torrance	California	United States	90509
9	Investigational Site	Savannah	Georgia	United States	31405
10	Investigational Site	Naperville	Illinois	United States	60540
11	Investigational Site	Indianapolis	Indiana	United States	46280
12	Investigational Site	Shreveport	Louisiana	United States	71103
13	Investigational Site	Columbus	Ohio	United States	43215
14	Investigational Site	Landsdale	Pennsylvania	United States	19446
15	Investigational Site	Tacoma	Washington	United States	98405
16	Investigational Site	Buenos Aires		Argentina	164
17	Investigational Site	Buenos Aires		Argentina
18	Invetigational Site	Buenos Aires		Argentina
19	Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	1240 C1180AAX
20	Investigational Site	Cordoba		Argentina
21	Invetigational Site	Cordoba		Argentina
22	Investigational Site	Entre Rios		Argentina
23	Investigational Site	Santa Fe		Argentina
24	Investigational Site	Curiuba-Parans		Brazil	1089
25	Investigational Site	Sao Paulo		Brazil	04039-020
26	Investigational Site	Santiago		Chile
27	Investigational Site	Vina del Mar		Chile
28	Investigational Site	Berlin		Germany	D-10249
29	Investigational Site	Bochum		Germany	44791
30	Investigational Site	Hanau		Germany
31	Investigational Site	Plauen		Germany	08529
32	Investigational Site	Quedlinburg		Germany	06484
33	Investigational Site	Chihuahua		Mexico	31238
34	Invetigational Site	Lima		Peru	29
35	Investigational Site	Bytom		Poland	41-902
36	Investigational Site	Krakow		Poland	31-913
37	Investigational Site	Lublin		Poland	20-081
38	Investigational Site	Sosnowiec		Poland	41-200
39	Investigational Site	Todz		Poland	91-425
40	Investigational Site	Bucharest		Romania	010816
41	Investigational Site	Bucharest		Romania	041915
42	Investigational Site	Timisoara		Romania	300736
43	Investigational Site	Moscow		Russian Federation	105229
44	Investigational Site	Moscow		Russian Federation	111539
45	Investigational Site	Moscow		Russian Federation	129327
46	Investigational Site	Smolensk		Russian Federation	214019
47	Investigational Site	St. Petersburg		Russian Federation	192242
48	Investigational Site	St. Petersburg		Russian Federation	194354
49	Investigational Site	St. Petersburg		Russian Federation	196247
50	Investigational Site	Dnipropetrovsk		Ukraine	49600
51	Investigational Site	Ivano-Frankivsk		Ukraine	76008
52	Investigational Site	Lviv		Ukraine	79659

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Principal Investigator: Ralph Corey, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00424190
• Other Study ID Numbers: P903-06
• First Posted: Jan 18, 2007
• Last Update Posted: Mar 14, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by , ,: Abscess; Antibacterial; Antibiotic; Antimicrobial; Bacterial infection, skin; Ceftaroline; Ceftaroline acetate; Cellulitis; Cephalosporin; Complicated skin and skin structure infection; cSSSI; Intravenous; Methicillin-resistant Staphylococcus Aureus (MRSA); PPI-0903; Prodrug; Skin disease, bacterial; Skin infection; Staphylococcal skin infection; Staphylococcus aureus; Streptococcal skin infection; Surgical site infection; TAK-599
• Additional relevant MeSH terms: Infections; Communicable Diseases; Bacterial Infections; Vancomycin; Ceftaroline fosamil; Aztreonam

Study Results

Participant Flow

Recruitment Details	Patients were recruited worldwide from February 2007 to November 2007
Pre-assignment Detail	Patients were screened for up to 24 hours

Arm/Group Title	Ceftaroline Fosamil for Injection	IV Vancomycin Plus IV Aztreonam
Arm/Group Description	Ceftaroline fosamil 600 mg administered IV over 60 minutes every 12 hours followed by placebo administered over 60 minutes every 12 hours	Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours
Period Title: Overall Study
STARTED	351	347
COMPLETED	329	317
NOT COMPLETED	22	30

Baseline Characteristics

Arm/Group Title	Ceftaroline Fosamil for Injection	IV Vancomycin Plus IV Aztreonam	Total
Arm/Group Description	Ceftaroline fosamil 600 mg administered IV over 60 minutes every 12 hours followed by placebo administered over 60 minutes every 12 hours	Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours	Total of all reporting groups
Overall Participants	351	347	698
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.2 (17.17)	47.2 (17.01)	48.2 (17.10)
Age, Customized (participants) [Number]
>=65 years	57 16.2%	72 20.7%	129 18.5%
<18 years	0 0%	0 0%	0 0%
>=18 years and < 65 years	294 83.8%	275 79.3%	569 81.5%
Sex: Female, Male (Count of Participants)
Female	131 37.3%	129 37.2%	260 37.2%
Male	220 62.7%	218 62.8%	438 62.8%
Race/Ethnicity, Customized (participants) [Number]
Non-Hispanic	268 76.4%	270 77.8%	538 77.1%
Hispanic	83 23.6%	77 22.2%	160 22.9%

Outcome Measures

1. Primary Outcome

Title	Clinical Cure Rate at Test of Cure (TOC) (MITT Population)
Description	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 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
Time Frame	8-15 days after the end of treatment

Outcome Measure Data

Analysis Population Description

MITT (Modified Intent to Treat) - Any randomized subjects that received any amount of study drug

Arm/Group Title	Ceftaroline Fosamil for Injection	IV Vancomycin Plus IV Aztreonam
Arm/Group Description	Ceftaroline fosamil 600 mg administered IV over 60 minutes every 12 hours followed by placebo administered over 60 minutes every 12 hours	Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours
Measure Participants	351	347
Clinical Cure	304 86.6%	297 85.6%
Clinical Failure	29 8.3%	21 6.1%
Indeterminate	18 5.1%	29 8.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ceftaroline Fosamil for Injection, IV Vancomycin Plus IV Aztreonam
	Comments	The primary objective of this study was to determine the noninferiority in clinical cure rate of ceftaroline in comparison with vancomycin plus aztreonam in adult subjects with cSSSI.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A two-sided 95% confidence interval (CI) for the observed difference in the primary outcome measure between ceftaroline and vancomycin plus aztreonam was calculated. Noninferiority was concluded if the lower limit of the 95% CI was higher than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -4.2 to 6.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference corresponds to Ceftaroline clinical cure rate minus Vancomycin plus Aztreonam clinical cure rate. The confidence interval was calculated using the Miettinen and Nurminen method without adjustment.

2. Primary Outcome

Title	Clinical Cure Rate of Ceftaroline Compared With That of Vancomycin Plus Aztreonam Treatment at TOC in the Clinically Evaluable (CE) Population
Time Frame	8-15 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Microbiological Success Rate at the TOC Visit
Time Frame	8-15 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Clinical Response at the End of Therapy (EOT) Visit
Time Frame	Last day of study drug administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Clinical and Microbiological Response by Pathogen at the TOC Visit
Time Frame	8-15 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Clinical Relapse at the Late Follow Up (LFU) Visit
Time Frame	21 to 35 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Microbiological Reinfection or Recurrence at the LFU Visit
Time Frame	21 to 35 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Assess Safety
Description	Comparisons of the number of participants with Adverse Events
Time Frame	First dose of study drug through TOC visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	All safety analysis was performed on the Safety Population, those subjects that had received any amount of the actual study drug.
Arm/Group Title	Ceftaroline Fosamil for Injection		IV Vancomycin Plus IV Aztreonam
Arm/Group Description	Ceftaroline fosamil 600 mg administered IV over 60 minutes every 12 hours followed by placebo administered over 60 minutes every 12 hours		Vancomycin 1 g administered over 60 minutes every 12 hours followed by aztreonam 1 g administered over 60 minutes every 12 hours
All Cause Mortality
	Ceftaroline Fosamil for Injection		IV Vancomycin Plus IV Aztreonam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ceftaroline Fosamil for Injection		IV Vancomycin Plus IV Aztreonam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/351 (4.6%)		12/347 (3.5%)
Cardiac disorders
Cardiac failure congestive	1/351 (0.3%)	1	1/347 (0.3%)	1
Cardiopulmonary failure	1/351 (0.3%)	1	0/347 (0%)	0
Coronary artery disease	0/351 (0%)	0	1/347 (0.3%)	1
Gastrointestinal disorders
Constipation	0/351 (0%)	0	1/347 (0.3%)	1
Hematochezia	1/351 (0.3%)	1	0/347 (0%)	0
Intestinal ischemia	1/351 (0.3%)	1	0/347 (0%)	0
Peptic ulcer hemorrhage	1/351 (0.3%)	1	0/347 (0%)	0
General disorders
Generalized edema	0/351 (0%)	0	1/347 (0.3%)	1
Immune system disorders
Hypersensitivity	1/351 (0.3%)	1	1/347 (0.3%)	1
Infections and infestations
Cellulitis	2/351 (0.6%)	2	1/347 (0.3%)	1
Clostridial infection	1/351 (0.3%)	1	0/347 (0%)	0
Osteomyelitis	1/351 (0.3%)	1	0/347 (0%)	0
Renal abscess	1/351 (0.3%)	1	0/347 (0%)	0
Viral infection	0/351 (0%)	0	1/347 (0.3%)	1
Wound infection	0/351 (0%)	0	1/347 (0.3%)	1
Investigations
Electrocardiogram ST segment elevation	1/351 (0.3%)	1	0/347 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	1/351 (0.3%)	1	0/347 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/351 (0.3%)	1	0/347 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma	0/351 (0%)	0	1/347 (0.3%)	1
Neoplasm malignant	1/351 (0.3%)	1	0/347 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/351 (0.3%)	1	0/347 (0%)	0
Syncope	0/351 (0%)	0	1/347 (0.3%)	1
Transient ischemic attack	0/351 (0%)	0	1/347 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Pleurisy	1/351 (0.3%)	1	0/347 (0%)	0
Respiratory failure	1/351 (0.3%)	1	0/347 (0%)	0
Vascular disorders
Arterial thrombosis limb	0/351 (0%)	0	1/347 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Ceftaroline Fosamil for Injection		IV Vancomycin Plus IV Aztreonam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	128/351 (36.5%)		162/347 (46.7%)
Gastrointestinal disorders
Nausea	20/351 (5.7%)	20	16/347 (4.6%)	16
Diarrhea	12/351 (3.4%)	12	11/347 (3.2%)	11
Vomiting	9/351 (2.6%)	9	9/347 (2.6%)	9
Constipation	8/351 (2.3%)	8	6/347 (1.7%)	6
General disorders
Pyrexia	4/351 (1.1%)	4	9/347 (2.6%)	9
Fatigue	1/351 (0.3%)	1	7/347 (2%)	7
Investigations
Aspartate aminotransferase increased	3/351 (0.9%)	3	7/347 (2%)	7
Nervous system disorders
Headache	18/351 (5.1%)	18	13/347 (3.7%)	13
Dizziness	8/351 (2.3%)	8	6/347 (1.7%)	6
Psychiatric disorders
Insomnia	5/351 (1.4%)	5	9/347 (2.6%)	9
Skin and subcutaneous tissue disorders
Pruritus generalized	13/351 (3.7%)	13	16/347 (4.6%)	16
Rash	12/351 (3.4%)	12	8/347 (2.3%)	8
Pruritus	11/351 (3.1%)	11	29/347 (8.4%)	29
Erythema	3/351 (0.9%)	3	9/347 (2.6%)	9
Vascular disorders
Hypertension	1/351 (0.3%)	1	7/347 (2%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.