Why carry out this study?
|
Vancomycin is often used for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive microorganisms; treatment with vancomycin may be problematic because of nephrotoxicity and often requires monitoring of renal function during treatment. |
We sought to determine whether dalbavancin, a long-acting antibiotic that can be administered as a single dose for a 2-week course of therapy and has been shown to be noninferior to vancomycin in clinical trials, is associated with nephrotoxicity when compared with vancomycin. |
What was learned from this study?
|
Dalbavancin has lower rates of nephrotoxicity compared with vancomycin in patients with ABSSSI, with no need to monitor renal function. |
Digital Features
Introduction
Methods
Studies
Study number and title | Treatment | Dose adjustments for renal insufficiencya |
---|---|---|
DUR001-301 (DISCOVER trial) NCT01339091 | ||
Phase 3, randomized, double-blind, double-dummy study to compare the efficacy and safety of dalbavancin to a comparator regimen (vancomycin with possible switch to orally administered linezolid) for the treatment of acute bacterial skin and skin structure infections [17] | Intravenously administered dalbavancin: 1000 mg on day 1, 500 mg on day 8, IV placebo q12h to match vancomycin, possible switch to oral placebo q12h after 3 days IV therapy, treatment duration 10–14 days IV comparator: intravenously administered vancomycin 1000 mg or 15 mg/kg q12h, IV placebo to match dalbavancin, possible switch to orally administered linezolid 600 mg q12h after 3 days IV vancomycin therapy, treatment duration 10–14 days | Intravenously administered dalbavancin doses reduced to 750 mg on day 1 and 375 mg on day 8 Intravenously administered vancomycin dose adjustments were based on CrCl values, renal function, and vancomycin serum concentration |
DUR001-302 (DISCOVER trial) NCT01431339 | ||
Phase 3, randomized, double-blind, double-dummy study to compare the efficacy and safety of dalbavancin to a comparator regimen (vancomycin with possible switch to orally administered linezolid) for the treatment of acute bacterial skin and skin structure infections [17] | Intravenously administered dalbavancin: 1000 mg on day 1, 500 mg on day 8, IV placebo q12h to match vancomycin, possible switch to oral placebo q12h after 3 days IV therapy, treatment duration 10–14 days IV comparator: intravenously administered vancomycin 1000 mg or 15 mg/kg q12h, IV placebo to match dalbavancin, possible switch to orally administered linezolid 600 mg q12h after 3 days IV vancomycin therapy, treatment duration 10–14 days | Intravenously administered dalbavancin doses reduced to 750 mg on day 1 and 375 mg on day 8 Intravenously administered vancomycin dose adjustments were based on CrCl values, renal function, and vancomycin serum concentration |
DUR001-303 NCT02127970 | ||
Phase 3b, double-blind, multicenter, randomized study to compare the efficacy and safety of single-dose dalbavancin to a two-dose regimen of dalbavancin for the treatment of acute bacterial skin and skin structure infections [16] | Intravenously administered dalbavancin, two-dose regimen: 1000 mg on day 1, 500 mg on day 8 Intravenously administered dalbavancin, single-dose regimen: 1500 mg on day 1, placebo to match dalbavancin on day 8 | Intravenously administered dalbavancin, two-dose regimen: 750 mg on day 1, 375 mg on day 8 Intravenously administered dalbavancin, single-dose regimen: 1000 mg on day 1 |
Adverse Events
Statistical Analysis
Results
Patients
Characteristic | DUR001-301 | DUR001-302 | DUR001-303 | ||
---|---|---|---|---|---|
Dalbavancin (n = 284) | Comparator (n = 284) | Dalbavancin (n = 368) | Comparator (n = 367) | Dalbavancin (n = 695) | |
Demographics | |||||
Mean (SD) age, years | 48.8 (15.4) | 48.9 (15.1) | 49.0 (16.5) | 51.4 (16.2) | 48.2 (14.8) |
Male, n (%) | 168 (59.2) | 173 (60.9) | 220 (59.8) | 201 (54.8) | 406 (58.4) |
Race, n (%)a | |||||
White | 261 (91.9) | 259 (91.2) | 326 (88.6) | 319 (86.9) | 621 (89.4) |
Black/African American | 15 (5.3) | 18 (6.3) | 13 (3.5) | 17 (4.6) | 59 (8.5) |
Asian | 1 (0.4) | 2 (0.7) | 26 (7.1) | 30 (8.2) | 4 (0.6) |
Mean (SD) BMI, kg/m2 | 29.9 (8.1) | 29.0 (7.0) | 28.8 (6.4) | 29.1 (7.3) | 28.9 (7.4) |
Prior medical history related to renal function, n (%) | |||||
Diabetes mellitusa | 42 (14.8) | 30 (10.5) | 34 (9.2) | 62 (16.9) | 78 (11.2) |
Acute renal failure | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Chronic renal failure | 1 (0.4) | 1 (0.4) | 1 (0.3) | 1 (0.3) | 0 (0.0) |
Acute kidney injury | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.1) |
Hypertension | 69 (24.3) | 81 (28.5) | 93 (25.3) | 101 (27.5) | 183 (26.3) |
Anemia | 9 (3.2) | 5 (1.8) | 9 (2.4) | 12 (3.3) | 11 (1.6) |
CrCl | |||||
< 30 mL/min, n (%) | 11 (3.9) | 8 (2.8) | 9 (2.4) | 7 (1.9) | 9 (1.3) |
Mean (SD), mL/min | 89.3 (37.1) | 91.8 (36.7) | 89.3 (35.8) | 92.5 (39.2) | 95.9 (36.3) |
Prior (within 30 days of study start) medications known to affect renal function, n (%) | |||||
Aminoglycoside antibiotics | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.3) | 0 (0.0) |
Beta lactam antibiotics | 1 (0.4) | 3 (1.1) | 7 (1.9) | 9 (2.5) | 22 (3.2) |
Ibuprofen | 8 (2.8) | 8 (2.8) | 12 (3.3) | 8 (2.2) | 14 (2.0) |
Metformin | 0 (0.0) | 1 (0.4) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Treatment-Emergent Adverse Events
Patients | Dalbavancin | Vancomycinc | P valued | ||
---|---|---|---|---|---|
Single dosea (N = 349) n/N1 (%) | Two dosesb (N = 998) n/N1 (%) | Totalb (N = 1347) n/N1 (%) | (N = 651) n/N2 (%) | ||
Patients (safety population) experiencing a TEAE (n/N) | 70/349 (20.1) | 283/998 (28.4) | 353/1347 (26.2) | 247/651 (37.9) | < 0.0001 |
All patients experiencing a TEAE | 69/345 (20.0) | 278/980 (28.4) | 347/1325 (26.2) | 25/54 (46.3) | 0.0011 |
TEAE leading to premature discontinuation of study drug | 5/345 (1.4) | 18/980 (1.8) | 23/1325 (1.7) | 0 | 0.3291 |
Drug-related TEAE | 24/345 (7.0) | 104/980 (10.6) | 128/1325 (9.7) | 3/54 (5.6) | 0.3134 |
Serious TEAE | 7/345 (2.0) | 21/980 (2.1) | 28/1325 (2.1) | 7/54 (13.0) | < 0.0001 |
Nephrotoxicity on therapye | |||||
All dalbavancin patients vs patients intravenously administered vancomycin only | 15/345 (4.3) | 34/980 (3.5) | 49/1325 (3.7) | 5/54 (9.3) | 0.039 |
Patients receiving IV treatment onlyf | NA | 1/58 (1.7) | 1/58 (1.7) | 5/54 (9.3) | 0.0781 |