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A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study.

Stryjewski ME, Lentnek A, O'Riordan W, Pullman J, Tambyah PA, Miró JM, Fowler VG, Barriere SL, Kitt MM, Corey GR - BMC Infect. Dis. (2014)

Bottom Line: Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality.Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms.Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Division of Infectious Diseases, Centro de Educación Médica e Investigaciones Clinicas (CEMIC) "Norberto Quirno", Av, Las Heras 2981, Office #3, Capital Federal (C1425ASG), Buenos Aires, Argentina. stryj001@fibertel.com.ar.

ABSTRACT

Background: Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia.

Methods: Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days.

Results: In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%).

Conclusions: This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647).

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Patient disposition into the study populations. More than one reason may be present for patients to be excluded from all-treated target and/or clinically evaluable populations. SAB, S. aureus bacteremia; TOC, test of cure.
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Figure 1: Patient disposition into the study populations. More than one reason may be present for patients to be excluded from all-treated target and/or clinically evaluable populations. SAB, S. aureus bacteremia; TOC, test of cure.

Mentions: A total of 60 patients were randomized in the study. Among those, 58 patients from 21 sites in five countries received at least one dose of study medication (AT population) (Table 1). Patients were enrolled in the U.S., Argentina, Spain, Singapore, and Hong Kong. Most patients were enrolled in the U.S. (73%). Figure 1 displays the disposition of patients into the study populations. Only one patient was included under the amendment allowing complicated bacteremia, received telavancin 10 mg/kg q 24 h for 24 days, and was discontinued due to an AE.


A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study.

Stryjewski ME, Lentnek A, O'Riordan W, Pullman J, Tambyah PA, Miró JM, Fowler VG, Barriere SL, Kitt MM, Corey GR - BMC Infect. Dis. (2014)

Patient disposition into the study populations. More than one reason may be present for patients to be excluded from all-treated target and/or clinically evaluable populations. SAB, S. aureus bacteremia; TOC, test of cure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4048626&req=5

Figure 1: Patient disposition into the study populations. More than one reason may be present for patients to be excluded from all-treated target and/or clinically evaluable populations. SAB, S. aureus bacteremia; TOC, test of cure.
Mentions: A total of 60 patients were randomized in the study. Among those, 58 patients from 21 sites in five countries received at least one dose of study medication (AT population) (Table 1). Patients were enrolled in the U.S., Argentina, Spain, Singapore, and Hong Kong. Most patients were enrolled in the U.S. (73%). Figure 1 displays the disposition of patients into the study populations. Only one patient was included under the amendment allowing complicated bacteremia, received telavancin 10 mg/kg q 24 h for 24 days, and was discontinued due to an AE.

Bottom Line: Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality.Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms.Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Division of Infectious Diseases, Centro de Educación Médica e Investigaciones Clinicas (CEMIC) "Norberto Quirno", Av, Las Heras 2981, Office #3, Capital Federal (C1425ASG), Buenos Aires, Argentina. stryj001@fibertel.com.ar.

ABSTRACT

Background: Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia.

Methods: Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days.

Results: In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%).

Conclusions: This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647).

Show MeSH
Related in: MedlinePlus