ATLAS1: 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: NCT00091819
• Collaborator: (none)
• Enrollment: 862
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 50.8

Study Details

Study Description

Brief Summary

Study 0017 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: 862 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: Jan 1, 2005
• Actual Primary Completion Date: Jun 1, 2006
• Actual Study Completion Date: Jun 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 q 12 hrs for up to 14 days.

Outcome Measures

Primary Outcome Measures

1. Clinical Response [7-14 days following end of antibiotic treatment]

   The Clinical Response for each patient was determined by the investigator by assessing a patient's clinical signs and symptoms at the specified evaluation 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 Methicillin Resistant Staphylococcus aureus (MRSA) 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 prior to randomization

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Paradise Valley Hospital, 2400 E. 4th Street	National City	California	United States	91950

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: NCT00091819
• Other Study ID Numbers: 0017
• First Posted: Sep 21, 2004
• Last Update Posted: Jan 16, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by , ,: staph; MRSA; cSSSI
• Additional relevant MeSH terms: Infections; Communicable Diseases; Cellulitis; Skin Diseases, Infectious; Staphylococcal Skin Infections; Vancomycin; Telavancin

Study Results

Participant Flow

Recruitment Details	Enrollment Period: 19 January 2005 to 12 June 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 Gram every 12 hours. The maximum allowable treatment period was 14 days.
Period Title: Overall Study
STARTED	429	433
COMPLETED	387	387
NOT COMPLETED	42	46

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 Gram every 12 hours. The maximum allowable treatment period was 14 days.	Total of all reporting groups
Overall Participants	426	429	855
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	337 79.1%	357 83.2%	694 81.2%
>=65 years	89 20.9%	72 16.8%	161 18.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (17.3)	48 (16.1)	48 (16.7)
Sex: Female, Male (Count of Participants)
Female	196 46%	181 42.2%	377 44.1%
Male	230 54%	248 57.8%	478 55.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	114 26.8%	97 22.6%	211 24.7%
Not Hispanic or Latino	312 73.2%	332 77.4%	644 75.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 0.7%	2 0.5%	5 0.6%
Asian	7 1.6%	9 2.1%	16 1.9%
Native Hawaiian or Other Pacific Islander	3 0.7%	9 2.1%	12 1.4%
Black or African American	59 13.8%	52 12.1%	111 13%
White	349 81.9%	353 82.3%	702 82.1%
More than one race	4 0.9%	3 0.7%	7 0.8%
Unknown or Not Reported	1 0.2%	1 0.2%	2 0.2%
Region of Enrollment (participants) [Number]
United States	306 71.8%	316 73.7%	622 72.7%
South Africa	11 2.6%	12 2.8%	23 2.7%
Australia	18 4.2%	15 3.5%	33 3.9%
Belgium	2 0.5%	0 0%	2 0.2%
Croatia	49 11.5%	51 11.9%	100 11.7%
Israel	15 3.5%	12 2.8%	27 3.2%
Malaysia	5 1.2%	4 0.9%	9 1.1%
Russian Federation	20 4.7%	19 4.4%	39 4.6%
Diabetes Status (Number) [Number]
Diabetic	94 22.1%	98 22.8%	192 22.5%
Not diabetic	332 77.9%	331 77.2%	663 77.5%

Outcome Measures

1. Primary Outcome

Title	Clinical Response
Description	The Clinical Response for each patient was determined by the investigator by assessing a patient's clinical signs and symptoms at the specified evaluation 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	7-14 days following end of antibiotic treatment

Outcome Measure Data

Analysis Population Description

Data for the all-treated (AT) population 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 Gram every 12 hours. The maximum allowable treatment period was 14 days.
Measure Participants	426	429
Cure	323 75.8%	321 74.8%
Not cured	52 12.2%	58 13.5%
Indeterminate	23 5.4%	16 3.7%
Missing	28 6.6%	34 7.9%

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	1.0
	Confidence Interval	() 95%; -4.8 to 6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Statistical analysis applies to "cure"

Adverse Events

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 Gram 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	31/426 (7.3%)		27/429 (6.3%)
Blood and lymphatic system disorders
Thrombocytopenia	0/426 (0%)		1/429 (0.2%)
Leukopenia	0/426 (0%)		1/429 (0.2%)
White Blood Cell Count Increased	0/426 (0%)		1/429 (0.2%)
Cardiac disorders
Myocardial Infarction	2/426 (0.5%)		0/429 (0%)
Angina Pectoris	1/426 (0.2%)		0/429 (0%)
Atrial fibrillation	0/426 (0%)		2/429 (0.5%)
Bradycardia	1/426 (0.2%)		1/429 (0.2%)
Cardio-Respiratory Arrest	0/426 (0%)		1/429 (0.2%)
Myocardial Ischaemia	1/426 (0.2%)		0/429 (0%)
Ventricular Arrhythmia	1/426 (0.2%)		0/429 (0%)
Cardiac failure	0/426 (0%)		1/429 (0.2%)
Cardiac failure congestive	0/426 (0%)		1/429 (0.2%)
Gastrointestinal disorders
Abdominal Pain	0/426 (0%)		2/429 (0.5%)
Upper Gastrointestinal Haemorrhage	0/426 (0%)		1/429 (0.2%)
General disorders
Chest Discomfort	1/426 (0.2%)		0/429 (0%)
Injection Site Cellulitis	1/426 (0.2%)		0/429 (0%)
Systemic Inflammatory Response Syndrome	1/426 (0.2%)		0/429 (0%)
Non-Cardiac Chest Pain	0/426 (0%)		1/429 (0.2%)
Pyrexia	0/426 (0%)		1/429 (0.2%)
Immune system disorders
Drug Hypersensitivity	1/426 (0.2%)		1/429 (0.2%)
Hypersensitivity	0/426 (0%)		1/429 (0.2%)
Infections and infestations
Osteomyelitis	1/426 (0.2%)		0/429 (0%)
Pneumonia	0/426 (0%)		1/429 (0.2%)
Bacteraemia	0/426 (0%)		1/429 (0.2%)
Cellulitis	0/426 (0%)		1/429 (0.2%)
Gastroenteritis	0/426 (0%)		1/429 (0.2%)
Pelvic Infection	0/426 (0%)		1/429 (0.2%)
Injury, poisoning and procedural complications
Ankle Fracture	1/426 (0.2%)		0/429 (0%)
Post-Procedural Haemorrhage	0/426 (0%)		1/429 (0.2%)
Procedural Hypotension	0/426 (0%)		1/429 (0.2%)
Investigations
Blood creatinine increased	0/426 (0%)		2/429 (0.5%)
International Normalised Ratio Increased	1/426 (0.2%)		0/429 (0%)
Metabolism and nutrition disorders
Hyperglycemia	0/426 (0%)		1/429 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian Cancer	1/426 (0.2%)		0/429 (0%)
Nervous system disorders
Cerebrovascular Accident	1/426 (0.2%)		0/429 (0%)
Coma Hepatic	0/426 (0%)		1/429 (0.2%)
Psychiatric disorders
Mental Status Changes	1/426 (0.2%)		0/429 (0%)
Schizophrenia, Paranoid Type	1/426 (0.2%)		0/429 (0%)
Renal and urinary disorders
Renal Failure Acute	1/426 (0.2%)		0/429 (0%)
Renal Insufficiency	1/426 (0.2%)		0/429 (0%)
Renal Impairment	2/426 (0.5%)		0/429 (0%)
Calculus Bladder	1/426 (0.2%)		0/429 (0%)
Urinary Tract Infection	0/426 (0%)		1/429 (0.2%)
Renal Vessel Disorder	0/426 (0%)		1/429 (0.2%)
Reproductive system and breast disorders
Ovarian Cyst	0/426 (0%)		1/429 (0.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	2/426 (0.5%)		2/429 (0.5%)
Respiratory Distress	2/426 (0.5%)		2/429 (0.5%)
Chronic Obstructive Airways Disease Exacerbated	1/426 (0.2%)		0/429 (0%)
Dyspnoea	0/426 (0%)		1/429 (0.2%)
Pulmonary Congestion	1/426 (0.2%)		0/429 (0%)
Respiratory Failure	1/426 (0.2%)		3/429 (0.7%)
Bronchitis	0/426 (0%)		1/429 (0.2%)
Skin and subcutaneous tissue disorders
Rash	1/426 (0.2%)		0/429 (0%)
Vascular disorders
Hypotension	1/426 (0.2%)		1/429 (0.2%)
Deep Vein Thrombosis	2/426 (0.5%)		0/429 (0%)
Peripheral Occlusive Disease	1/426 (0.2%)		0/429 (0%)
Varicose Vein Ruptured	1/426 (0.2%)		0/429 (0%)
Other (Not Including Serious) Adverse Events
	Telavancin		Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	358/426 (84%)		335/429 (78.1%)
Blood and lymphatic system disorders
Anemia	12/426 (2.8%)		8/429 (1.9%)
Cardiac disorders
Angina Pectoris	5/426 (1.2%)		1/429 (0.2%)
Bradycardia	2/426 (0.5%)		5/429 (1.2%)
Cardiac failure congestive	5/426 (1.2%)		2/429 (0.5%)
Palpitations	6/426 (1.4%)		3/429 (0.7%)
Eye disorders
Vision blurred	5/426 (1.2%)		3/429 (0.7%)
Gastrointestinal disorders
Abdominal Distension	5/426 (1.2%)		4/429 (0.9%)
Abdominal pain	11/426 (2.6%)		17/429 (4%)
Abdominal pain upper	5/426 (1.2%)		8/429 (1.9%)
Constipation	61/426 (14.3%)		37/429 (8.6%)
Diarrhoea	31/426 (7.3%)		41/429 (9.6%)
Dry Mouth	11/426 (2.6%)		15/429 (3.5%)
Dyspepsia	14/426 (3.3%)		16/429 (3.7%)
Loose stools	5/426 (1.2%)		7/429 (1.6%)
Nausea	128/426 (30%)		95/429 (22.1%)
Vomiting	78/426 (18.3%)		50/429 (11.7%)
General disorders
Asthenia	8/426 (1.9%)		9/429 (2.1%)
Fatigue	19/426 (4.5%)		21/429 (4.9%)
Infusion site erythema	7/426 (1.6%)		9/429 (2.1%)
Infusion site pain	21/426 (4.9%)		21/429 (4.9%)
Infusion site phlebitis	6/426 (1.4%)		7/429 (1.6%)
Infusion site pruritis	5/426 (1.2%)		9/429 (2.1%)
Infusion site reaction	7/426 (1.6%)		7/429 (1.6%)
Lethargy	6/426 (1.4%)		1/429 (0.2%)
Non-Cardiac Chest Pain	12/426 (2.8%)		7/429 (1.6%)
Oedema Peripheral	8/426 (1.9%)		11/429 (2.6%)
Pain	4/426 (0.9%)		7/429 (1.6%)
Pyrexia	9/426 (2.1%)		10/429 (2.3%)
Rigors	22/426 (5.2%)		14/429 (3.3%)
Infections and infestations
Fungal Infection	5/426 (1.2%)		2/429 (0.5%)
Osteomyelitis	5/426 (1.2%)		4/429 (0.9%)
Pneumonia	5/426 (1.2%)		1/429 (0.2%)
Urinary Tract Infection	6/426 (1.4%)		4/429 (0.9%)
Vaginal candidiasis	5/426 (1.2%)		0/429 (0%)
Vaginal mycosis	5/426 (1.2%)		6/429 (1.4%)
Metabolism and nutrition disorders
Anorexia	10/426 (2.3%)		10/429 (2.3%)
Decreased appetite	13/426 (3.1%)		17/429 (4%)
Hypoglycaemia	11/426 (2.6%)		8/429 (1.9%)
Hypokalemia	1/426 (0.2%)		7/429 (1.6%)
Hypomagnesaemia	1/426 (0.2%)		6/429 (1.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/426 (2.8%)		8/429 (1.9%)
Back Pain	14/426 (3.3%)		8/429 (1.9%)
Muscle Cramp	5/426 (1.2%)		6/429 (1.4%)
Pain in Extremity	8/426 (1.9%)		7/429 (1.6%)
Nervous system disorders
Dizziness	27/426 (6.3%)		35/429 (8.2%)
Dysgeusia	156/426 (36.6%)		31/429 (7.2%)
Headache	82/426 (19.2%)		69/429 (16.1%)
Hypoaesthesia	3/426 (0.7%)		5/429 (1.2%)
Paresthesia	3/426 (0.7%)		5/429 (1.2%)
Psychiatric disorders
Agitation	4/426 (0.9%)		6/429 (1.4%)
Anxiety	18/426 (4.2%)		14/429 (3.3%)
Confusional State	7/426 (1.6%)		4/429 (0.9%)
Insomnia	71/426 (16.7%)		53/429 (12.4%)
Restlessness	4/426 (0.9%)		6/429 (1.4%)
Renal and urinary disorders
Dysuria	7/426 (1.6%)		5/429 (1.2%)
Haematuria	6/426 (1.4%)		0/429 (0%)
Renal Insufficiency	5/426 (1.2%)		1/429 (0.2%)
Urinary Incontinence	6/426 (1.4%)		3/429 (0.7%)
Urinary Abnormality	69/426 (16.2%)		8/429 (1.9%)
Reproductive system and breast disorders
Genital Pruritis Female	8/426 (1.9%)		6/429 (1.4%)
Respiratory, thoracic and mediastinal disorders
Cough	12/426 (2.8%)		13/429 (3%)
Dyspnoea	10/426 (2.3%)		7/429 (1.6%)
Pharyngolaryngeal Pain	15/426 (3.5%)		13/429 (3%)
Productive Cough	1/426 (0.2%)		5/429 (1.2%)
Skin and subcutaneous tissue disorders
Dry Skin	6/426 (1.4%)		11/429 (2.6%)
Erythema	6/426 (1.4%)		13/429 (3%)
Exanthem	7/426 (1.6%)		4/429 (0.9%)
Hyperhidrosis	10/426 (2.3%)		9/429 (2.1%)
Pruritis	25/426 (5.9%)		58/429 (13.5%)
Pruritis generalized	19/426 (4.5%)		40/429 (9.3%)
Rash	17/426 (4%)		23/429 (5.4%)
Rash generalized	1/426 (0.2%)		9/429 (2.1%)
Vascular disorders
Hot Flush	2/426 (0.5%)		7/429 (1.6%)
Hypertension	6/426 (1.4%)		7/429 (1.6%)
Hypotension	12/426 (2.8%)		7/429 (1.6%)

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.