EFFICACY

  • Telavancin is a lipoglycopeptide antibacterial agent and the first of a new class of antibiotics. It has dual bactericidal action, inhibiting cell wall synthesis and disrupting bacterial cell membrane function 1

  • Telavancin is active against Gram-positive bacteria only 2
  • Vibativ® (telavancin) successfully achieved its primary endpoint vs. vancomycin in two randomised, phase III non-inferiority studies of patients with hospital acquired pneumonia caused by Gram-positive bacteria 2
  • Clinical cure rates with telavancin were superior to vancomycin in patients with monomicrobial S. aureus infection with reduced susceptibility to vancomycin (MIC ≥1mg/l) (87% vs. 74%; p=0.03) 2
  • In line with its indication, a post-hoc analysis was carried out in patients without renal insufficiency at baseline 3
  • Telavancin achieved higher clinical cure rates vs. vancomycin in patients with only Gram-positive pathogens (85% vs. 75%;9.7% difference; 95% CI: 0.6-18.8%) 2,3

TELAVACIN EFFICACY IN HOSPITAL ACQUIRED PNEUMONIA (HAP)

The efficacy of Vibativ® (telavancin) has been assessed in two methodologically identical, non-inferiority, double-blind studies in comparison to vancomycin, in patients with hospital-acquired pneumonia (HAP) due to gram-positive bacteria (ATTAIN). 2

In the pooled analysis of these data, the primary endpoint of the study was met – illustrating that telavancin is non-inferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens. 2

Furthermore, telavancin demonstrated higher cure rates vs. vancomycin in patients from the microbiologically evaluable (ME) population with monomicrobial S. aureus pneumonia (almost 300 patients).  e.g. 84.2% (n = 146) vs 74.3% (n=152), p <0.05

Secondary analysis, excluding patients with severe renal impairment and acute renal failure, corroborated these data, indicating that patients from the ME population, with only gram-positive pathogens (isolated at baseline) had higher cure rates when treated with telavancin (85%, 130/153) compared to vancomycin (75.2%, 109/145). 3

Post-hoc analysis for consistency with the draft guidance issued by the US FDA for trials of treatments for nosocomial pneumonia, clinical cure plus 28 day survival also showed telavancin to be superior to vancomycin in this sub-set of patients (83.7% versus 71.7% respectively). 3

THE ATTAIN STUDIES

In total, 1532 patients were randomised to each treatment group (telavancin or vancomycin, 1:1). Sub-populations were determined based on the suitability of further evaluation as follows, all-treated patients (N=1503), clinically evaluable (CE) patients (N=654) and microbiologically evaluable (ME) patients (N=480). 2

In the pooled, all-treated population, cure rates with telavancin vs. vancomycin were similar; 58.9% vs. 59.5% (95% CI for the difference -5.6% to 4.3%). 2

In the pooled, CE population, cure rates with telavancin vs. vancomycin were similar; 82.4% vs. 80.7% (95% CI for the difference -4.3% to 7.7%). 2

To date, the ATTAIN studies represent one of the largest phase-III clinical trials involving a substantial population of MRSA infected patients. 2

Renal function should be monitored in all patients receiving telavancin. 1

The dose  of telavancin was adjusted for patients with reduced renal clearance and is recommended by the SPC.  1

EXCLUDING DATA FROM PATIENTS WITH SEVERE RENAL IMPAIRMENT AND ACUTE RENAL FAILURE

Current European prescribing information for telavancin contraindicates its use in patients with severe renal impairment (creatine clearance <30mL/min, including patients on haemodialysis) and acute renal failure.

As such, a post-hoc analysis of the ATTAIN population (N=1503) was carried out, excluding patients with severe renal impairment as defined above. This analysis included 84.2% of the original study population (1266/1503). 3

The findings were in-line with the ATTAIN study; cure rates in the CE population were similar in the telavancin (82.5%, 231/280) and vancomycin (81.3%, 243/299) groups. Patients from the ME population, with only gram-positive pathogens (isolated at baseline) had higher cure rates when treated with telavancin (85%, 130/153) compared to vancomycin (75.2%, 109/145). 3

Analysis for consistency with the draft guidance issued by the US FDA for trials of treatments for nosocomial pneumonia, clinical cure plus 28 day survival also showed telavancin to be superior to vancomycin in this sub-set of patients [(83.7% versus 71.7% respectively); treatment difference (95% Cl): 11.8% (2.4% - 21.3%)]

 

 

TOLERABILITY

The incidence of adverse events (AEs) was similar between telavancin and vancomycin treated populations. In the pooled analysis of the ATTAIN population, the mortality rate at end of follow up was 20.0% (150/751) in the telavancin group and 18.6% (140/752) in the vancomycin group. 2

The most common treatment-emergent AEs (TEAEs) in both groups were diarrhoea, anaemia, hypokalaemia, constipation and renal impairment. 2

The rate of discontinuations of study medication in the telavancin and vancomycin groups for serious AEs (SAEs) were 31% and 26% respectively; for TEAEs these rates were 8% and 5% respectively. 2

Tolerability outcomes were similar in the post-hoc analysis, excluding patients with severe renal impairment. 3

Data considerations

During the course of the study, participating centres were allowed to adjust the dose of vancomycin in accordance with their internal guidance, whilst maintaining the blind. Approximately 65% of patients had their vancomycin dose adjusted.  It was permitted to decrease the dose of telavancin where patients showed decreased creatinine clearance. 2

The mean age of the study population was 62 years and as stated in the summary of product characteristics (SPC)  the safety and efficacy of telavancin in children aged less than 18 years of age have not been established.

References
  1. Vibativ SPC - Clinigen Healthcare Ltd - Updated July 2014
  2. Rubinstein E, Lalani T, Corey GR et al. Telavancin versus Vancomycin for Hospital-Acquired Pneumonia due to Gram-positive Pathogens. Clinical Infectious Diseases, 2011; 52(1): 31-40
  3. Torres A, Rubinstein E, Corey GR et al. Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure. Journal of Antimicrobial Chemotherapy. 2014 Apr,69(4):1119 - 26.doi:10.1093/jac.dkt490.Epub 2014 Jan 6
  4. Scott LJ. Telavancin: A Review of its use in patients with nosocomial pneumonia. Drugs, 2013 73:1829 - 1839