ASSURE: Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia

• Sponsor: Cumberland Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00062647
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether telavancin (TD-6424, ARBELIC) can be safety administered to patients with bloodstream infections and whether telavancin is effective in treating these infections.

Condition or Disease	Intervention/Treatment	Phase
Gram-Positive Bacterial Infections	Drug: Telavancin; Drug: Vancomycin, nafcillin, oxacillin, or cloxacillin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 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, Parallel-Group, Multinational Trial of Intravenous Televancin (TD-6424) for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Aug 1, 2006
• Actual Study Completion Date: Aug 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Telavancin	Drug: Telavancin; Telavancin 10mg/kg/day IV every 24 hrs for up to 14 days; Other Names: TD-6424 VIBATIV
Active Comparator: Vancomycin, nafcillin, oxacillin, or cloxacillin Vancomycin 1 Gram/12 hours or nafcillin, oxacillin, or cloxacillin 2 Gram/6 hours (IV) intravenously	Drug: Vancomycin, nafcillin, oxacillin, or cloxacillin; Vancomycin 1 Gram every 12 hr IV (intravenously) OR nafcillin, oxacillin, or cloxacillin 2 Grams every 6 hr IV (intravenously) for up to 14 days.

Outcome Measures

Primary Outcome Measures

1. Clinical Response (Cure, Failure, or Indeterminate) as Determined by the Investigator Based the Presence or Absence of Clinical Signs and Symptoms Associated With Bacteremia, Metastatic Complications, or Positive Culture at the Test of Cure Evaluation [12 weeks after start of treatment]

   Outcomes in this exploratory study were compared for noninferiority though no specific margin was justified. The 95% CI for the difference was -35.5 to 31.9; further statistical evaluation is not warranted owing to the small sample size.

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Documented S. aureus bacteremia

Exclusion Criteria

• Patients who had received or would have received more than 72 hours of potentially effective systemic antistaphylococcal therapy within 7 days prior to randomization. The following agents were considered potentially effective antistaphylococcal therapy: antistaphylococcal penicillins (including nafcillin, oxacillin, or cloxacillin), cephalosporins, fluoroquinolones, glycopeptides (including vancomycin and teicoplanin) and linezolid

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wellstar Infectious Disease	Marietta	Georgia	United States	30060

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: NCT00062647
• Other Study ID Numbers: I6424-203a
• First Posted: Jun 12, 2003
• Last Update Posted: Jan 16, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Bacterial Infections; Bacteremia; Gram-Positive Bacterial Infections; Vancomycin; Cloxacillin; Oxacillin; Telavancin; Nafcillin

Study Results

Participant Flow

Recruitment Details	Enrollment period: 14 Aug 2003 to 02 Aug 2006

Arm/Group Title	Telavancin	Standard Therapy
Arm/Group Description	Patients with uncomplicated Staphylococcus aureus bacteremia were randomized to receive telavancin 10 mg/kg/day IV (intravenously) every 12 hrs for up to 14 days. Excludes 1 patient who never started therapy.	Patients with uncomplicated Staphylococcus aureus bacteremia were randomized to receive vancomycin 1 Gram IV (intravenously) every 12 hrs OR nafcillin, oxacillin, or cloxacillin 2 Gram IV (intravenously) every 6 hrs for up to 14 days. Excludes one patient who never started therapy.
Period Title: Overall Study
STARTED	30	30
COMPLETED	14	17
NOT COMPLETED	16	13

Baseline Characteristics

Arm/Group Title	Telavancin	Standard Therapy	Total
Arm/Group Description	Patients with uncomplicated Staphylococcus aureus bacteremia were randomized to receive telavancin 10 mg/kg/day IV (intravenously) every 12 hrs for up to 14 days. Excludes 1 patient who never started therapy.	Patients with uncomplicated Staphylococcus aureus bacteremia were randomized to receive vancomycin 1 Gram IV (intravenously) every 12 hrs OR nafcillin, oxacillin, or cloxacillin 2 Gram IV (intravenously) every 6 hrs for up to 14 days. Excludes one patient who never started therapy.	Total of all reporting groups
Overall Participants	29	29	58
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 62.1%	18 62.1%	36 62.1%
>=65 years	11 37.9%	11 37.9%	22 37.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (19)	60 (17.9)	60 (17.9)
Sex: Female, Male (Count of Participants)
Female	11 37.9%	14 48.3%	25 43.1%
Male	18 62.1%	15 51.7%	33 56.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 24.1%	7 24.1%	14 24.1%
Not Hispanic or Latino	22 75.9%	22 75.9%	44 75.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.4%	1 3.4%	2 3.4%
Asian	2 6.9%	4 13.8%	6 10.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 31%	3 10.3%	12 20.7%
White	17 58.6%	21 72.4%	38 65.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Argentina	3 10.3%	2 6.9%	5 8.6%
Singapore	1 3.4%	3 10.3%	4 6.9%
Spain	2 6.9%	3 10.3%	5 8.6%
United States	22 75.9%	21 72.4%	43 74.1%
Hong Kong	1 3.4%	0 0%	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Clinical Response (Cure, Failure, or Indeterminate) as Determined by the Investigator Based the Presence or Absence of Clinical Signs and Symptoms Associated With Bacteremia, Metastatic Complications, or Positive Culture at the Test of Cure Evaluation
Description	Outcomes in this exploratory study were compared for noninferiority though no specific margin was justified. The 95% CI for the difference was -35.5 to 31.9; further statistical evaluation is not warranted owing to the small sample size.
Time Frame	12 weeks after start of treatment

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis was of the CE Population, defined as those patients meeting meeting inclusion/exclusion criteria, meeting continuation criteria, receiving assigned study drug for at least 14 days and available for assessment of response.

Arm/Group Title	Telavancin	Standard Therapy
Arm/Group Description	Patients with uncomplicated Staphylococcus aureus bacteremia were randomized to receive telavancin 10 mg/kg/day IV (intravenously) every 12 hrs for up to 14 days. Excludes 1 patient who never started therapy.	Patients with uncomplicated Staphylococcus aureus bacteremia were randomized to receive vancomycin 1 Gram IV (intravenously) every 12 hrs OR nafcillin, oxacillin, or cloxacillin 2 Gram IV (intravenously) every 6 hrs for up to 14 days. Excludes one patient who never started therapy.
Measure Participants	8	9
Cured	7 24.1%	8 27.6%
Failure	1 3.4%	1 3.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Telavancin, Standard Therapy
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	No margin was justified owing to the exploratory nature of the investigation.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1
	Confidence Interval	() 95%; -35.5 to 31.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From receipt of first dose through last follow-up assessment (up to Day 98).
Arm/Group Title	Telavancin		Standard Therapy
Arm/Group Description	Patients with uncomplicated Staphylococcus aureus bacteremia were randomized to receive telavancin 10 mg/kg/day IV (intravenously) every 12 hrs for up to 14 days. Excludes 1 patient who never started therapy.		Patients with uncomplicated Staphylococcus aureus bacteremia were randomized to receive vancomycin 1 Gram IV (intravenously) every 12 hrs OR nafcillin, oxacillin, or cloxacillin 2 Gram IV (intravenously) every 6 hrs for up to 14 days. Excludes one patient who never started therapy.
All Cause Mortality
	Telavancin		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Telavancin		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/29 (37.9%)		6/29 (20.7%)
Cardiac disorders
Endocarditis bacterial	1/29 (3.4%)	1	0/29 (0%)	0
Gastrointestinal disorders
Abdominal Pain	0/29 (0%)	0	1/29 (3.4%)	1
Nausea	0/29 (0%)	0	1/29 (3.4%)	1
Vomiting	0/29 (0%)	0	1/29 (3.4%)	1
General disorders
Adverse Drug Reaction	1/29 (3.4%)	1	0/29 (0%)	0
Death	1/29 (3.4%)	1	0/29 (0%)	0
Multi-organ Failure	1/29 (3.4%)	1	1/29 (3.4%)	1
Neuroleptic Malignant Syndrome	0/29 (0%)	0	1/29 (3.4%)	1
Pyrexia	1/29 (3.4%)	1	0/29 (0%)	0
Immune system disorders
Hypersensitivity	0/29 (0%)	0	1/29 (3.4%)	1
Infections and infestations
Endocarditis	0/29 (0%)	0	1/29 (3.4%)	1
Lobar Pneumonia	1/29 (3.4%)	1	0/29 (0%)	0
Sepsis	1/29 (3.4%)	1	1/29 (3.4%)	1
Investigations
Blood creatinine increased	0/29 (0%)	0	1/29 (3.4%)	1
Metabolism and nutrition disorders
Dehydration	0/29 (0%)	0	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Back Pain	0/29 (0%)	0	1/29 (3.4%)	1
Nervous system disorders
Neuropathy peripheral	1/29 (3.4%)	1	0/29 (0%)	0
Syncope vasovagal	1/29 (3.4%)	1	0/29 (0%)	0
Psychiatric disorders
Mental Status Changes	1/29 (3.4%)	1	0/29 (0%)	0
Renal and urinary disorders
Renal Failure Acute	1/29 (3.4%)	1	0/29 (0%)	0
Renal Failure Chronic	1/29 (3.4%)	1	0/29 (0%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/29 (3.4%)	1	0/29 (0%)	0
Dyspnoea	1/29 (3.4%)	1	1/29 (3.4%)	1
Pleural Effusion	1/29 (3.4%)	1	0/29 (0%)	0
Respiratory Tract Congestion	1/29 (3.4%)	1	0/29 (0%)	0
Vascular disorders
Deep Vein Thrombosis	1/29 (3.4%)	1	0/29 (0%)	0
Other (Not Including Serious) Adverse Events
	Telavancin		Standard Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/29 (89.7%)		21/29 (72.4%)
Blood and lymphatic system disorders
Anemia	3/29 (10.3%)	3	2/29 (6.9%)	2
Eosinophilia	0/29 (0%)	0	2/29 (6.9%)	2
Gastrointestinal disorders
Diarrhoea	0/29 (0%)	0	2/29 (6.9%)	2
Nausea	1/29 (3.4%)	1	2/29 (6.9%)	2
Vomiting	1/29 (3.4%)	1	2/29 (6.9%)	2
General disorders
Catheter site erythema	2/29 (6.9%)	2	1/29 (3.4%)	1
Pyrexia	3/29 (10.3%)	3	2/29 (6.9%)	2
Infections and infestations
Catheter site infection	0/29 (0%)	0	2/29 (6.9%)	2
Urinary Tract Infection	2/29 (6.9%)	2	0/29 (0%)	0
Urinary Tract Infection Fungal	2/29 (6.9%)	2	0/29 (0%)	0
Investigations
Blood Urea increased	2/29 (6.9%)	2	0/29 (0%)	0
Eosinophil Count increased	0/29 (0%)	0	2/29 (6.9%)	2
Metabolism and nutrition disorders
Hypokalemia	3/29 (10.3%)	3	1/29 (3.4%)	1
Nervous system disorders
Dysgeusia	3/29 (10.3%)	3	0/29 (0%)	0
Headache	3/29 (10.3%)	3	3/29 (10.3%)	3
Psychiatric disorders
Agitation	2/29 (6.9%)	2	1/29 (3.4%)	1
Insomnia	2/29 (6.9%)	2	1/29 (3.4%)	1
Renal and urinary disorders
Haematuria	1/29 (3.4%)	1	2/29 (6.9%)	2
Skin and subcutaneous tissue disorders
Pruritis	1/29 (3.4%)	1	2/29 (6.9%)	2
Rash pruritic	0/29 (0%)	0	2/29 (6.9%)	2
Vascular disorders
Deep Vein Thrombosis	3/29 (10.3%)	3	1/29 (3.4%)	1
Phlebitis	1/29 (3.4%)	1	2/29 (6.9%)	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.