ATLAS2: Comparison of Telavancin and Vancomycin for Complicated Skin and Skin Structure Infections With a Focus on Methicillin-resistant Staphylococcus Aureus

• Sponsor: Cumberland Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00107978
• Collaborator: (none)
• Enrollment: 1,035
• Location: 1
• Arms: 2
• Duration (Months): 14.9
• Patients Per Site Per Month: 69.4

Study Details

Study Description

Brief Summary

Study 0018 (NCT00107978) compares the safety and effectiveness of an investigational drug, telavancin, and an approved drug, vancomycin, for the treatment of complicated skin and skin structure infections.

Condition or Disease	Intervention/Treatment	Phase
Staphylococcal Skin Infection	Drug: Telavancin; Drug: Vancomycin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1035 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Multinational Trial of Intravenous Telavancin Versus Vancomycin for Treatment of Complicated Gram Positive Skin and Skin Structure Infections With a Focus on Patients With Infections Due to Methicillin-resistant Staphylococcus Aureus
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: May 1, 2006
• Actual Study Completion Date: May 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Telavancin	Drug: Telavancin; Telavancin 10 mg/kg/day, IV for up to 14 days.; Other Names: VIBATIV TD-6424
Active Comparator: Vancomycin	Drug: Vancomycin; Vancomycin 1 Gm IV administered every 12 hrs for up to 14 days.

Outcome Measures

Primary Outcome Measures

1. Clinical Response [7 to 14 days after the last antibiotic dose]

   The Clinical Response for each patient was determined by the investigator by assessing the patient's clinical signs & symptoms compared with the Baseline evaluation. Cure: resolution of signs and symptoms associated with the skin infection present at study admission such that no further antibiotic therapy was necessary; Not Cured: inadequate response to study therapy; Indeterminate: unable to determine outcome.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have a diagnosis of one of the following complicated skin and skin structure infections with MRSA (Methicillin-resistant Staphylococcus Aureus) either suspected or confirmed as the major cause of the infection:

• major abscess requiring surgical incision and drainage;

• infected burn (see exclusion criteria for important qualifications);

• deep/extensive cellulitis;

• infected ulcer (see exclusion criteria for important qualifications);

• wound infections

• Patients must be expected to require at least 7 days of intravenous antibiotic treatment.

Exclusion Criteria:

• Received more than 24 hours of potentially effective systemic (IV/IM or PO) antibiotic therapy

• Burns involving > 20% of body surface area or third degree/full thickness in nature, diabetic foot ulcers, ischemic ulcers/wounds, necrotizing fasciitis, gas gangrene, or mediastinitis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Louisiana State University Health Sciences Center, Dept of Med/ER Med	New Orleans	Louisiana	United States	70112

Sponsors and Collaborators

• Cumberland Pharmaceuticals

Investigators

• Principal Investigator: G. Ralph Corey, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00107978
• Other Study ID Numbers: 0018
• First Posted: Apr 12, 2005
• Last Update Posted: Jan 16, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by , ,: cSSSI (complicated Skin and Skin Structure Infections); Staph (Staphylococcus); MRSA (Methicillin-resistant Staphylococcus Aureus)
• Additional relevant MeSH terms: Infections; Communicable Diseases; Staphylococcal Infections; Cellulitis; Skin Diseases, Infectious; Staphylococcal Skin Infections; Vancomycin; Telavancin

Study Results

Participant Flow

Recruitment Details	Enrollment Period: 18 February 2005 to 31 May 2006

Arm/Group Title	Telavancin	Vancomycin
Arm/Group Description	Patients with complicated Gram-positive skin and skin structure infections (primarily due to MRSA) were randomized to receive telavancin 10 mg/kg IV once daily. The maximum allowable treatment period was 14 days.	Patients with complicated Gram-positive skin and skin structure infections (primarily due to MRSA) were randomized to receive vancomycin 1 Gm every 12 hours. The maximum allowable treatment period was 14 days.
Period Title: Overall Study
STARTED	458	481
COMPLETED	425	431
NOT COMPLETED	33	50

Baseline Characteristics

Arm/Group Title	Telavancin	Vancomycin	Total
Arm/Group Description	Patients with complicated Gram-positive skin and skin structure infections (primarily due to MRSA) were randomized to receive telavancin 10 mg/kg IV once daily. The maximum allowable treatment period was 14 days.	Patients with complicated Gram-positive skin and skin structure infections (primarily due to MRSA) were randomized to receive vancomycin 1 Gm every 12 hours. The maximum allowable treatment period was 14 days.	Total of all reporting groups
Overall Participants	458	481	939
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	377 82.3%	379 78.8%	756 80.5%
>=65 years	81 17.7%	102 21.2%	183 19.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.2 (16.1)	49.9 (17.0)	49.5 (16.6)
Sex: Female, Male (Count of Participants)
Female	200 43.7%	187 38.9%	387 41.2%
Male	258 56.3%	294 61.1%	552 58.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	79 17.2%	84 17.5%	163 17.4%
Not Hispanic or Latino	379 82.8%	397 82.5%	776 82.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	7 1.5%	9 1.9%	16 1.7%
Asian	38 8.3%	44 9.1%	82 8.7%
Native Hawaiian or Other Pacific Islander	4 0.9%	8 1.7%	12 1.3%
Black or African American	69 15.1%	74 15.4%	143 15.2%
White	336 73.4%	343 71.3%	679 72.3%
More than one race	4 0.9%	3 0.6%	7 0.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	287 62.7%	310 64.4%	597 63.6%
South Africa	6 1.3%	6 1.2%	12 1.3%
Argentina	35 7.6%	33 6.9%	68 7.2%
Canada	35 7.6%	29 6%	64 6.8%
Chile	1 0.2%	2 0.4%	3 0.3%
France	0 0%	2 0.4%	2 0.2%
Germany	0 0%	4 0.8%	4 0.4%
Italy	2 0.4%	1 0.2%	3 0.3%
Korea, Republic of	14 3.1%	16 3.3%	30 3.2%
Lithuania	12 2.6%	6 1.2%	18 1.9%
Peru	4 0.9%	1 0.2%	5 0.5%
Poland	38 8.3%	43 8.9%	81 8.6%
Spain	2 0.4%	3 0.6%	5 0.5%
Taiwan	20 4.4%	25 5.2%	45 4.8%
United Kingdom	2 0.4%	0 0%	2 0.2%
Diabetes Status (Number) [Number]
Diabetic	113 24.7%	118 24.5%	231 24.6%
Not diabetic	345 75.3%	363 75.5%	708 75.4%

Outcome Measures

1. Primary Outcome

Title	Clinical Response
Description	The Clinical Response for each patient was determined by the investigator by assessing the patient's clinical signs & symptoms compared with the Baseline evaluation. Cure: resolution of signs and symptoms associated with the skin infection present at study admission such that no further antibiotic therapy was necessary; Not Cured: inadequate response to study therapy; Indeterminate: unable to determine outcome.
Time Frame	7 to 14 days after the last antibiotic dose

Outcome Measure Data

Analysis Population Description

Data for the all-treated population (AT) are presented. The AT and clinically evaluable (CE) populations were considered co-primary.

Arm/Group Title	Telavancin	Vancomycin
Arm/Group Description	Patients with complicated Gram-positive skin and skin structure infections (primarily due to MRSA) were randomized to receive telavancin 10 mg/kg IV once daily. The maximum allowable treatment period was 14 days.	Patients with complicated Gram-positive skin and skin structure infections (primarily due to MRSA) were randomized to receive vancomycin 1 Gm every 12 hours. The maximum allowable treatment period was 14 days.
Measure Participants	458	481
Cure	358	364
Not cured	59	57
Indeterminate	17	20
Missing	24	40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Telavancin, Vancomycin
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin of 10% was specified based on historical regulatory precedent.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.5
	Confidence Interval	() 95%; -2.9 to 7.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	Safety data includes data from all patients treated. Efficacy data does not include data from three sites. Hence, there is a discrepancy between the total numbers of patients in each arm in the safety data vs. the efficacy data.
Arm/Group Title	Telavancin		Vancomycin
Arm/Group Description	Patients with complicated Gram-positive skin and skin structure infections (primarily due to MRSA) were randomized to receive telavancin 10 mg/kg IV once daily. The maximum allowable treatment period was 14 days.		Patients with complicated Gram-positive skin and skin structure infections (primarily due to MRSA) were randomized to receive vancomycin 1 Gm every 12 hours. The maximum allowable treatment period was 14 days.
All Cause Mortality
	Telavancin		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Telavancin		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/503 (7.6%)		15/509 (2.9%)
Blood and lymphatic system disorders
Anemia	3/503 (0.6%)		0/509 (0%)
Cardiac disorders
Myocardial Infarction	2/503 (0.4%)		1/509 (0.2%)
Atrial fibrillation	0/503 (0%)		1/509 (0.2%)
Cardiac Arrest	1/503 (0.2%)		1/509 (0.2%)
Cardio-Respiratory Arrest	1/503 (0.2%)		0/509 (0%)
Acute Myocardial Infarction	0/503 (0%)		1/509 (0.2%)
Cardiac failure	0/503 (0%)		1/509 (0.2%)
Cardiogenic Shock	0/503 (0%)		1/509 (0.2%)
Gastrointestinal disorders
Diarrhoea	1/503 (0.2%)		0/509 (0%)
Ascites	0/503 (0%)		1/509 (0.2%)
General disorders
Malaise	1/503 (0.2%)		0/509 (0%)
Infusion site reaction	0/503 (0%)		1/509 (0.2%)
Pyrexia	0/503 (0%)		1/509 (0.2%)
Rigors	0/503 (0%)		1/509 (0.2%)
Hepatobiliary disorders
Cholecystitis	1/503 (0.2%)		0/509 (0%)
Hepatic Cirrhosis	1/503 (0.2%)		0/509 (0%)
Immune system disorders
Drug Hypersensitivity	2/503 (0.4%)		1/509 (0.2%)
Anaphylactic Reaction	1/503 (0.2%)		0/509 (0%)
Hypersensitivity	1/503 (0.2%)		0/509 (0%)
Infections and infestations
Osteomyelitis	1/503 (0.2%)		0/509 (0%)
Pneumonia	2/503 (0.4%)		1/509 (0.2%)
Abscess Soft Tissue	1/503 (0.2%)		0/509 (0%)
Sepsis	1/503 (0.2%)		1/509 (0.2%)
Urinary Tract Infection	1/503 (0.2%)		0/509 (0%)
Gastrointestinal Infection	0/503 (0%)		1/509 (0.2%)
Septic Shock	0/503 (0%)		1/509 (0.2%)
Injury, poisoning and procedural complications
Non-Accidental Overdose	1/503 (0.2%)		0/509 (0%)
Soft Tissue Injury	0/503 (0%)		1/509 (0.2%)
Investigations
Blood creatinine increased	3/503 (0.6%)		0/509 (0%)
Blood Urea increased	2/503 (0.4%)		0/509 (0%)
Alanine Aminotransferase increased	0/503 (0%)		1/509 (0.2%)
Aspartate Aminotransferase increased	0/503 (0%)		1/509 (0.2%)
Metabolism and nutrition disorders
Dehydration	2/503 (0.4%)		0/509 (0%)
Hypoglycaemia	1/503 (0.2%)		0/509 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral Discitis	1/503 (0.2%)		0/509 (0%)
Hip Fracture	0/503 (0%)		1/509 (0.2%)
Pain in Extremity	0/503 (0%)		1/509 (0.2%)
Nervous system disorders
Brain Stem Infarction	1/503 (0.2%)		0/509 (0%)
Psychiatric disorders
Mental Status Changes	2/503 (0.4%)		0/509 (0%)
Renal and urinary disorders
Renal Failure Acute	3/503 (0.6%)		0/509 (0%)
Renal Insufficiency	2/503 (0.4%)		0/509 (0%)
Nephrolithiasis	1/503 (0.2%)		0/503 (0%)
Renal Failure Chronic	0/503 (0%)		1/509 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	2/503 (0.4%)		0/509 (0%)
Alveolitis Allergic	1/503 (0.2%)		0/509 (0%)
Dyspnoea	1/503 (0.2%)		0/509 (0%)
Pulmonary Oedema	0/503 (0%)		1/509 (0.2%)
Skin and subcutaneous tissue disorders
Rash	1/503 (0.2%)		0/509 (0%)
Erythema Multiforme	1/503 (0.2%)		0/509 (0%)
Vascular disorders
Hypotension	1/503 (0.2%)		0/509 (0%)
Peripheral Occlusive Disease	1/503 (0.2%)		0/509 (0%)
Gangrene	1/503 (0.2%)		0/509 (0%)
Orthostatic Hypotension	1/503 (0.2%)		0/509 (0%)
Peripheral Ischaemia	0/503 (0%)		1/509 (0.2%)
Other (Not Including Serious) Adverse Events
	Telavancin		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	377/503 (75%)		341/509 (67%)
Blood and lymphatic system disorders
Anemia	11/503 (2.2%)		10/509 (2%)
Gastrointestinal disorders
Abdominal Pain	6/503 (1.2%)		9/509 (1.8%)
Constipation	35/503 (7%)		24/509 (4.7%)
Diarrhoea	36/503 (7.2%)		35/509 (6.9%)
Dry Mouth	9/503 (1.8%)		7/509 (1.4%)
Dyspepsia	7/503 (1.4%)		7/509 (1.4%)
Loose stools	6/503 (1.2%)		6/509 (1.2%)
Nausea	121/503 (24.1%)		47/509 (9.2%)
Vomiting	49/503 (9.7%)		19/509 (3.7%)
General disorders
Asthenia	5/503 (1%)		7/509 (1.4%)
Fatigue	22/503 (4.4%)		10/509 (2%)
Infusion site erythema	17/503 (3.4%)		15/509 (2.9%)
Infusion site pain	20/503 (4%)		19/509 (3.7%)
Infusion site phlebitis	12/503 (2.4%)		14/509 (2.8%)
Infusion site pruritis	4/503 (0.8%)		9/509 (1.8%)
Infusion site reaction	7/503 (1.4%)		7/509 (1.4%)
Pyrexia	6/503 (1.2%)		2/509 (0.4%)
Rigors	19/503 (3.8%)		7/509 (1.4%)
Immune system disorders
Drug Hypersensitivity	5/503 (1%)		6/509 (1.2%)
Infections and infestations
Urinary Tract Infection	13/503 (2.6%)		3/509 (0.6%)
Vaginal mycosis	4/503 (0.8%)		6/509 (1.2%)
Investigations
Alanine Aminotransferase increased	6/503 (1.2%)		13/509 (2.6%)
Aspartate Aminotransferase increased	6/503 (1.2%)		10/509 (2%)
Blood Creatinine Increased	9/503 (1.8%)		3/509 (0.6%)
Metabolism and nutrition disorders
Anorexia	7/503 (1.4%)		1/509 (0.2%)
Decreased appetite	12/503 (2.4%)		2/509 (0.4%)
Hypoglycaemia	7/503 (1.4%)		3/509 (0.6%)
Hypokalaemia	9/503 (1.8%)		12/509 (2.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/503 (1.4%)		5/509 (1%)
Back pain	6/503 (1.2%)		9/509 (1.8%)
Nervous system disorders
Dizziness	28/503 (5.6%)		18/509 (3.5%)
Dysgeusia	155/503 (30.8%)		31/509 (6.1%)
Headache	48/503 (9.5%)		51/509 (10%)
Hypoaesthesia	3/503 (0.6%)		6/509 (1.2%)
Paraesthesia	3/503 (0.6%)		7/509 (1.4%)
Somnolence	8/503 (1.6%)		3/509 (0.6%)
Psychiatric disorders
Anxiety	8/503 (1.6%)		8/509 (1.6%)
Insomnia	19/503 (3.8%)		33/509 (6.5%)
Renal and urinary disorders
Renal Failure Acute	6/503 (1.2%)		0/509 (0%)
Urine Abnormality	53/503 (10.5%)		19/509 (3.7%)
Respiratory, thoracic and mediastinal disorders
Cough	5/503 (1%)		7/509 (1.4%)
Pharyngolaryngeal Pain	7/503 (1.4%)		5/509 (1%)
Skin and subcutaneous tissue disorders
Erythema	3/503 (0.6%)		6/509 (1.2%)
Pruritis	29/503 (5.8%)		62/509 (12.2%)
Pruritis generalized	9/503 (1.8%)		20/509 (3.9%)
Rash	18/503 (3.6%)		20/509 (3.9%)
Urticaria	4/503 (0.8%)		7/509 (1.4%)
Vascular disorders
Flushing	6/503 (1.2%)		14/509 (2.8%)
Hypertension	6/503 (1.2%)		6/509 (1.2%)
Hypotension	5/503 (1%)		6/509 (1.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.