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ATLAS 2: a double-blind, randomised, active controlled, multinational Phase 3 study comparing telavancin with vancomycin for the treatment of patients with complicated skin and skin structure infections
Abstract number: 1733_344
Corey G.R., Stryjewski M.E., Fowler Jr V.G., Teglia O., Hopkins A., Kitt M.M., Barriere for the ATLAS Study Group S.L.
Objectives: Telavancin is a novel, rapidly bactericidal lipoglycopeptide with activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). It has a multifunctional mechanism of action, which includes inhibiting cell wall synthesis and disrupting plasma membrane functional integrity. The efficacy and safety of telavancin vs vancomycin have been compared in patients with complicated skin and skin structure infections (cSSSIs) in two Phase 3 studies. Here we report results from the second of these trials, ATLAS 2. Methods: ATLAS 2 was a double-blind, randomised, active controlled, multinational study involving men and women, aged 18 years or older. Patients had a cSSSI (major abscess, infected burn, deep/extensive cellulitis, infected ulcer or wound infection) requiring ≥7 days of IV antibiotic therapy. Patients were randomised to IV infusions of telavancin 10 mg/kg once daily or vancomycin 1 g once every 12 h for 7–14 days. The primary efficacy endpoint was the clinical response at the test-of-cure visit (7–14 days after the last dose of study drug), evaluated using non-inferiority criteria (with a non-inferiority delta of 10%). Secondary endpoints included clinical cure in patients with MRSA infections, clinical cure by pathogen and microbiological eradication. Safety was also evaluated. Clinical cure and microbiological eradication at test-of-cure clinic visit | Endpoint | Cure rate |
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| Telavancin, n (%) | Vancomycin, n (%) | Difference, % (95% CI) | |
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| Clinical cure | | All-treated population | 387/502 (77.1) | 376/510 (73.7) | 3.4 (-1.9, 8.7) | | Clinically evaluable population | 354/399 (88.7) | 346/395 (87.6) | 1.1 (-3.4, 5.6) | | Clinically evaluable population (MRSA) | 151/162 (93.2) | 142/163 (87.1) | 6.1 (-0.3, 12.5) | | Microbiological eradication | | Modified all-treated population | 287/373 (76.9) | 285/38 (74.8) | 2.1 (-4.0, 8.2) | | Microbiologically evaluable population | 261/290 (90.0) | 249/281 (88.6) | 1.4 (-3.7, 6.5) | | Microbiologically evaluable population (MRSA) | 149/162 (92.0) | 140/163 (85.9) | 6.1 (-0.7, 12.9) | | Overall therapeutic response (cure + eradication) | | Modified all-treated population | 281/373 (75.3) | 276/381 (72.4) | 2.9 (-3.4, 9.2) | | Microbiologically evaluable population | 257/290 (88.6) | 244/281 (86.8) | 1.8 (-3.6, 7.2) | | Microbiologically evaluable population (MRSA) | 149/162 (92.0) | 138/163 (84.7) | 7.3 (0.4, 14.2) |
Results: A total of 502 patients received telavancin (n = 399 clinically evaluable; n = 290 microbiologically evaluable; n = 204 with MRSA) and 510 received vancomycin (n = 395 clinically evaluable; n = 281 microbiologically evaluable; n = 202 with MRSA). Clinical cure and eradication at the test-of-cure visit were similar for the two treatments (Table), demonstrating the non-inferiority of telavancin vs vancomycin, since the lower bound of the 95% confidence interval was greater than -10%. Telavancin achieved a higher overall therapeutic response (cure + eradication) than vancomycin. Adverse events were comparable in the two treatment arms. Overall, 43 (8.6%) telavancin-treated patients and 28 (5.5%) vancomycin-treated patients discontinued due to adverse events. Conclusion: In the ATLAS 2 study, telavancin was found to be effective for the treatment of patients with cSSSIs, including those caused by MRSA. The results, including overall therapeutic response, consistently favoured telavancin compared with vancomycin. Telavancin also had an acceptable adverse event profile for the treatment of serious infections due to resistant bacteria.
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