FAST: Phase 2 Trial of TD 6424 (Telavancin) Versus Standard Therapy for Complicated Gram Positive Skin and Skin Structure Infections (Gram Positive cSSSI)

• Sponsor: Cumberland Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00061633
• Collaborator: (none)
• Enrollment: 169
• Location: 1
• Arms: 2
• Duration (Months): 7
• Patients Per Site Per Month: 24

Study Details

Study Description

Brief Summary

Serious infections caused by resistant bacteria are becoming more of a medical problem throughout the world. One of the ways to deal with this problem is to develop new drugs that can control these bacteria. This study will measure how well TD-6424 (Telavancin) can control infections and whether this drug can be safely given to patients.

Condition or Disease	Intervention/Treatment	Phase
Infections, Gram-Positive Bacterial; Abscess; Burns; Cellulitis; Ulcer; Wound Infections	Drug: Telavancin; Drug: Vancomycin or antistaphylococcal penicillin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 169 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Multinational Trial of Intravenous Telavancin Versus Standard Therapy for Treatment of Complicated Gram Positive Skin and Skin Structure Infections (Gram Positive cSSSI)
• Study Start Date: Jun 1, 2003
• Actual Primary Completion Date: Jan 1, 2004
• Actual Study Completion Date: Jan 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Telavancin	Drug: Telavancin; Telavancin 7.5 mg/kg/day IV (intravenously) for up to 14 days; Other Names: VIBATIV TD-6424
Active Comparator: Standard of care for cSSSI cSSSI - complicated skin and skin structure infections	Drug: Vancomycin or antistaphylococcal penicillin; Vancomycin 1 Gram IV (intravenously) every 12 hrs or nafcillin 2 Grams, oxacillin 2 Grams, or (in South Africa) cloxacillin 0.5 - 1 Gram, IV (intravenously) every 6 hrs for up to 14 days.

Outcome Measures

Primary Outcome Measures

1. Clinical Response Which is Measured at Test of Cure (TOC) in the Clinically Evaluable (CE) Population [7-14 days following end of antibiotic treatment]

   Cure: Resolution of clinically significant signs, symptoms associated with the skin infection present at study admission or improvement to the extent that the infectious process had been controlled and no further therapy with study medication was necessary. Failure: Inadequate response to study therapy or the need for significant surgical management (e.g. more than just routine debridement) of the infection site following antibiotic therapy and prior to the Test-of-Cure (TOC) visit. Indeterminate: Inability 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 either a suspected or confirmed Gram positive organism 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 4 days of intravenous antibiotic treatment

Exclusion Criteria:

• Previous systemic antibacterial therapy (with the exception of aztreonam and metronidazole) for > 24 hours within 7 days prior to the first dose of study medication unless the pathogen was resistant to prior treatment or the patient was a treatment failure (no clinical improvement after 3 days).

• 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	eStudy Site, 3450 Bonita Road, Ste 201	Chula Vista	California	United States	91910

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: NCT00061633
• Other Study ID Numbers: I6424-202a
• First Posted: Jun 2, 2003
• Last Update Posted: Jan 16, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Infections; Communicable Diseases; Wound Infection; Cellulitis; Gram-Positive Bacterial Infections; Vancomycin; Penicillins; Telavancin

Study Results

Participant Flow

Recruitment Details	Enrollment Period: 05Jun03 to 20Jan04

Arm/Group Title	Telavancin	Standard of Care for cSSSI
Arm/Group Description	Patients with complicated Gram-positive skin and skin structure infections were randomized to receive telavancin 10 mg/kg/day IV (intravenously)	Patients with complicated Gram-positive skin and skin structure infections were randomized to receive standard therapy, defined as vancomycin 1 Gram every 12 hours IV (intravenously) or an antistaphylococcal (semisynthetic) penicillin.
Period Title: Overall Study
STARTED	84	85
COMPLETED	79	74
NOT COMPLETED	5	11

Baseline Characteristics

Arm/Group Title	Telavancin	Standard of Care for cSSSI	Total
Arm/Group Description	Patients with complicated Gram-positive skin and skin structure infections were randomized to receive telavancin 10 mg/kg/day IV (intravenously)	Patients with complicated Gram-positive skin and skin structure infections were randomized to receive standard therapy, defined as vancomycin 1 Gram every 12 hours IV (intravenously) or an antistaphylococcal (semisynthetic) penicillin.	Total of all reporting groups
Overall Participants	84	83	167
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	80 95.2%	78 94%	158 94.6%
>=65 years	4 4.8%	5 6%	9 5.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.6 (13.9)	44.3 (13.5)	44.4 (13.7)
Sex: Female, Male (Count of Participants)
Female	30 35.7%	37 44.6%	67 40.1%
Male	54 64.3%	46 55.4%	100 59.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 17.9%	10 12%	25 15%
Not Hispanic or Latino	68 81%	72 86.7%	140 83.8%
Unknown or Not Reported	1 1.2%	1 1.2%	2 1.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.2%	1 0.6%
Asian	4 4.8%	1 1.2%	5 3%
Native Hawaiian or Other Pacific Islander	6 7.1%	5 6%	11 6.6%
Black or African American	21 25%	20 24.1%	41 24.6%
White	38 45.2%	41 49.4%	79 47.3%
More than one race	13 15.5%	14 16.9%	27 16.2%
Unknown or Not Reported	2 2.4%	1 1.2%	3 1.8%
Region of Enrollment (participants) [Number]
United States	59 70.2%	58 69.9%	117 70.1%
South Africa	25 29.8%	25 30.1%	50 29.9%
Diabetes Status (participants) [Number]
Diabetic	25 29.8%	19 22.9%	44 26.3%
Non-Diabetic	59 70.2%	64 77.1%	123 73.7%

Outcome Measures

1. Primary Outcome

Title	Clinical Response Which is Measured at Test of Cure (TOC) in the Clinically Evaluable (CE) Population
Description	Cure: Resolution of clinically significant signs, symptoms associated with the skin infection present at study admission or improvement to the extent that the infectious process had been controlled and no further therapy with study medication was necessary. Failure: Inadequate response to study therapy or the need for significant surgical management (e.g. more than just routine debridement) of the infection site following antibiotic therapy and prior to the Test-of-Cure (TOC) visit. Indeterminate: Inability to determine outcome.
Time Frame	7-14 days following end of antibiotic treatment

Outcome Measure Data

Analysis Population Description

The CE population were a subset of the All Treated Population and was composed of patients who met the inclusion/exclusion criteria or were granted permission to enroll and had a clinical response of "cure" or "failure." The All Treated Population patients received at least one treatment. The Primary Efficacy Analysis was of the CE population.

Arm/Group Title	Telavancin	Standard of Care for cSSSI
Arm/Group Description	Patients with complicated Gram-positive skin and skin structure infections were randomized to receive telavancin 10 mg/kg/day IV (intravenously)	Patients with complicated Gram-positive skin and skin structure infections were randomized to receive standard therapy, defined as vancomycin 1 Gram every 12 hours IV (intravenously) or an antistaphylococcal (semisynthetic) penicillin.
Measure Participants	72	69
Cured	66 78.6%	66 79.5%
Failure	6 7.1%	3 3.6%
Indeterminate	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Telavancin, Standard of Care for cSSSI
	Comments	95% Confidence Interval: -0.1349 to 0.0485 No est. value. Parameter that was estimated: Risk Difference
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Sample size was selected on the basis of clinical judgment and was deemed adequate to provide clinically meaningful descriptive results consistent with study objectives. This sample size was estimated to provide 39% power to test televancin's non-inferiority to vancomycin with respect to clinical response using a non-inferiority margin of 10%.
Statistical Test of Hypothesis	p-Value	0.5289
	Comments
	Method	2-sided 95% confidence interval
	Comments

Adverse Events

Adverse Event Reporting Description	The Safety Population was the "All Treated Population" - all patients who received one treatment. The Primary Analysis was of the Clinically Evaluable (CE) Population. The CE population was composed of the patients who met the inclusion / exclusion criteria or were granted permission to enroll and had a clinical response of "cure" or "failure".
Arm/Group Title	Telavancin		Standard of Care for cSSSI
Arm/Group Description	Patients with complicated Gram-positive skin and skin structure infections were randomized to receive telavancin 10 mg/kg/day IV (intravenously)		Patients with complicated Gram-positive skin and skin structure infections were randomized to receive standard therapy, defined as vancomycin 1 Gram every 12 hours IV (intravenously) or an antistaphylococcal (semisynthetic) penicillin.
All Cause Mortality
	Telavancin		Standard of Care for cSSSI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Telavancin		Standard of Care for cSSSI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/84 (3.6%)		9/83 (10.8%)
Infections and infestations
Cellulitis	0/84 (0%)		3/83 (3.6%)
Necrotizing Fasciitis	1/84 (1.2%)		0/83 (0%)
Subcutaneous Abscess	0/84 (0%)		1/83 (1.2%)
Wound Abscess	0/84 (0%)		1/83 (1.2%)
Wound Infection	1/84 (1.2%)		0/83 (0%)
Injury, poisoning and procedural complications
Wound dehiscence	0/84 (0%)		1/83 (1.2%)
Musculoskeletal and connective tissue disorders
Inguinal mass	0/84 (0%)		1/83 (1.2%)
Reproductive system and breast disorders
Vaginal Haemorrhage	0/84 (0%)		1/83 (1.2%)
Skin and subcutaneous tissue disorders
Angioneurotic Oedema	0/84 (0%)		1/83 (1.2%)
Vascular disorders
Gangrene	1/84 (1.2%)		0/83 (0%)
Other (Not Including Serious) Adverse Events
	Telavancin		Standard of Care for cSSSI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/84 (54.8%)		50/83 (60.2%)
Blood and lymphatic system disorders
Anemia	2/84 (2.4%)		1/83 (1.2%)
Leukopenia	1/84 (1.2%)		0/83 (0%)
Cardiac disorders
Arrhythmia	1/84 (1.2%)		0/83 (0%)
Atrial fibrillation	0/84 (0%)		1/83 (1.2%)
Eye disorders
Keratoconjunctivitis Sicca	1/84 (1.2%)		0/83 (0%)
Gastrointestinal disorders
Abdominal Pain	2/84 (2.4%)		1/83 (1.2%)
Abdominal pain upper	0/84 (0%)		2/83 (2.4%)
Constipation	3/84 (3.6%)		5/83 (6%)
Diarrhoea	1/84 (1.2%)		2/83 (2.4%)
Dry Mouth	1/84 (1.2%)		0/83 (0%)
Dyspepsia	2/84 (2.4%)		0/83 (0%)
Dysphasia	0/84 (0%)		1/83 (1.2%)
Nausea	13/84 (15.5%)		11/83 (13.3%)
Post-Procedural Nausea	0/84 (0%)		1/83 (1.2%)
Retching	0/84 (0%)		1/83 (1.2%)
Toothache	2/84 (2.4%)		0/83 (0%)
Vomiting	8/84 (9.5%)		3/83 (3.6%)
General disorders
Anasarca	1/84 (1.2%)		0/83 (0%)
Catheter related complication	0/84 (0%)		1/83 (1.2%)
Catheter Site Inflammation	1/84 (1.2%)		0/83 (0%)
Catheter site rash	0/84 (0%)		1/83 (1.2%)
Chest Pain	0/84 (0%)		1/83 (1.2%)
Discomfort	1/84 (1.2%)		1/83 (1.2%)
Drug Withdrawal Syndrome	1/84 (1.2%)		1/83 (1.2%)
Fatigue	2/84 (2.4%)		0/83 (0%)
Feeling hot	2/84 (2.4%)		1/83 (1.2%)
Feeling jittery	0/84 (0%)		1/83 (1.2%)
Infusion site pain	1/84 (1.2%)		1/83 (1.2%)
Injection Site Extravasation	0/84 (0%)		1/83 (1.2%)
Injection site phlebitis	0/84 (0%)		1/83 (1.2%)
Oedema Peripheral	1/84 (1.2%)		1/83 (1.2%)
Pain	1/84 (1.2%)		0/83 (0%)
Pain exacerbated	1/84 (1.2%)		0/83 (0%)
Pyrexia	3/84 (3.6%)		1/83 (1.2%)
Red Man Syndrome	0/84 (0%)		3/83 (3.6%)
Rigors	1/84 (1.2%)		1/83 (1.2%)
Infections and infestations
Abscess	1/84 (1.2%)		0/83 (0%)
Bacteriuria	3/84 (3.6%)		0/83 (0%)
Cellulitis	0/84 (0%)		3/83 (3.6%)
Gonorrhea	1/84 (1.2%)		0/83 (0%)
Influenza	1/84 (1.2%)		1/83 (1.2%)
Localized Infection	1/84 (1.2%)		0/83 (0%)
Nasal abscess	0/84 (0%)		1/83 (1.2%)
Necrotizing Fasciitis	1/84 (1.2%)		0/83 (0%)
Subcutaneous Abscess	0/84 (0%)		1/83 (1.2%)
Superinfection	1/84 (1.2%)		1/83 (1.2%)
Tuberculosis	1/84 (1.2%)		0/83 (0%)
Upper Respiratory Infection	0/84 (0%)		1/83 (1.2%)
Urinary Tract Infection	4/84 (4.8%)		4/83 (4.8%)
Vaginal Candidiasis	1/84 (1.2%)		0/83 (0%)
Wound Abscess	0/84 (0%)		1/83 (1.2%)
Wound infection staphylococcal	1/84 (1.2%)		0/83 (0%)
Injury, poisoning and procedural complications
Tinea Pedis	0/84 (0%)		1/83 (1.2%)
Blister	1/84 (1.2%)		0/83 (0%)
Ligament Injury	1/84 (1.2%)		0/83 (0%)
Muscle Strain	0/84 (0%)		1/83 (1.2%)
Wound dehiscence	0/84 (0%)		1/83 (1.2%)
Investigations
Alanine Aminotransferase increased	0/84 (0%)		4/83 (4.8%)
Aspartate Aminotransferase increased	1/84 (1.2%)		6/83 (7.2%)
Blood Alkaline phosphatase increased	1/84 (1.2%)		1/83 (1.2%)
Blood creatinine increased	1/84 (1.2%)		0/83 (0%)
Blood glucose decreased	0/84 (0%)		1/83 (1.2%)
Blood in stool	0/84 (0%)		1/83 (1.2%)
Blood lactate dehydrogenase increased	2/84 (2.4%)		3/83 (3.6%)
Blood pressure increased	1/84 (1.2%)		0/83 (0%)
Body temperature increased	1/84 (1.2%)		0/83 (0%)
Gamma-glutamyltransferase increased	2/84 (2.4%)		1/83 (1.2%)
Hepatic Enzyme increased	0/84 (0%)		1/83 (1.2%)
HIV Test positive	1/84 (1.2%)		0/83 (0%)
Liver function test abnormal	1/84 (1.2%)		1/83 (1.2%)
Metabolism and nutrition disorders
Anorexia	0/84 (0%)		3/83 (3.6%)
Diabetes Mellitus	1/84 (1.2%)		0/83 (0%)
Hyperglycaemia	0/84 (0%)		2/83 (2.4%)
Hypoglycaemia	1/84 (1.2%)		0/83 (0%)
Hypokalaemia	3/84 (3.6%)		0/83 (0%)
Hypomagnesaemia	2/84 (2.4%)		3/83 (3.6%)
Hyponatremia	0/84 (0%)		1/83 (1.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/84 (1.2%)		0/83 (0%)
Back Pain	1/84 (1.2%)		3/83 (3.6%)
Inguinal mass	0/84 (0%)		1/83 (1.2%)
Neck Pain	0/84 (0%)		1/83 (1.2%)
Pain in Extremity	0/84 (0%)		3/83 (3.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine Leiomyoma	0/84 (0%)		1/83 (1.2%)
Nervous system disorders
Burning sensation	2/84 (2.4%)		0/83 (0%)
Dizziness	2/84 (2.4%)		1/83 (1.2%)
Headache	9/84 (10.7%)		8/83 (9.6%)
Hypoaesthesia	1/84 (1.2%)		0/83 (0%)
Migraine	0/84 (0%)		1/83 (1.2%)
Paraesthesia	3/84 (3.6%)		0/83 (0%)
Somnolence	1/84 (1.2%)		1/83 (1.2%)
Tremor	1/84 (1.2%)		0/83 (0%)
Psychiatric disorders
Agitation	2/84 (2.4%)		3/83 (3.6%)
Anxiety	6/84 (7.1%)		2/83 (2.4%)
Confusional State	0/84 (0%)		1/83 (1.2%)
Depression	1/84 (1.2%)		1/83 (1.2%)
Disorientation	0/84 (0%)		1/83 (1.2%)
Euphoric Mood	1/84 (1.2%)		0/83 (0%)
Insomnia	0/84 (0%)		4/83 (4.8%)
Irritability	1/84 (1.2%)		1/83 (1.2%)
Restlessness	0/84 (0%)		1/83 (1.2%)
Schizophrenia	1/84 (1.2%)		0/83 (0%)
Renal and urinary disorders
Albuminuria	0/84 (0%)		1/83 (1.2%)
Diabetic neuropathy	0/84 (0%)		1/83 (1.2%)
Haematuria	1/84 (1.2%)		1/83 (1.2%)
Microalbuminuria	4/84 (4.8%)		1/83 (1.2%)
Urinary Incontinence	1/84 (1.2%)		1/83 (1.2%)
Reproductive system and breast disorders
Genital Pruritis Female	0/84 (0%)		1/83 (1.2%)
Vaginal Haemorrhage	0/84 (0%)		1/83 (1.2%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/84 (1.2%)		0/83 (0%)
Cough	3/84 (3.6%)		1/83 (1.2%)
Crackles Lung	2/84 (2.4%)		0/83 (0%)
Dyspnoea	5/84 (6%)		1/83 (1.2%)
Hiccups	1/84 (1.2%)		0/83 (0%)
Rhonchi	1/84 (1.2%)		0/83 (0%)
Wheezing	1/84 (1.2%)		2/83 (2.4%)
Skin and subcutaneous tissue disorders
Acne	1/84 (1.2%)		0/83 (0%)
Angioneurotic Oedema	0/84 (0%)		1/83 (1.2%)
Dermatitis contact	0/84 (0%)		1/83 (1.2%)
Dry Skin	0/84 (0%)		2/83 (2.4%)
Erythema	1/84 (1.2%)		0/83 (0%)
Hyperhidrosis	0/84 (0%)		1/83 (1.2%)
Night sweats	1/84 (1.2%)		0/83 (0%)
Photosensitivity Reaction	0/84 (0%)		1/83 (1.2%)
Pruritis	3/84 (3.6%)		1/83 (1.2%)
Rash	2/84 (2.4%)		2/83 (2.4%)
Rash pruritic	0/84 (0%)		1/83 (1.2%)
Skin Burning sensation	0/84 (0%)		1/83 (1.2%)
Skin Irritation	0/84 (0%)		1/83 (1.2%)
Skin Ulcer	1/84 (1.2%)		0/83 (0%)
Urticaria	0/84 (0%)		1/83 (1.2%)
Vascular disorders
Flushing	0/84 (0%)		1/83 (1.2%)
Gangrene	1/84 (1.2%)		0/83 (0%)
Hot Flush	0/84 (0%)		1/83 (1.2%)
Hypertension	1/84 (1.2%)		0/83 (0%)
Hypotension	3/84 (3.6%)		1/83 (1.2%)
Peripheral Ischaemia	1/84 (1.2%)		0/83 (0%)
Phlebitis	0/84 (0%)		1/83 (1.2%)
Thrombophlebitis	1/84 (1.2%)		2/83 (2.4%)

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.