TABLE 14.
Clinical studies assessing imipenem-relebactam
| Trial ID (reference) | Comparatora | Phase | Designb | No. of patientsc | Indicationd | Exclusion of immunocompromised patients | Bacteriae | Outcomesf
|
|
|---|---|---|---|---|---|---|---|---|---|
| No. (%) interventions vs control | Risk difference (95% CIs) | ||||||||
| Motsch 2019 (227) | Col+Imi | 3 | RCT, Noninferential | 47 p (31 I-R, 16 Col+Imi) | NP, cUTI, cIAI | Immunocompromised allowed | P. aeruginosa: 31p (77%), 24 i (42% ceftazidimer, 54% Meror) | Mortality: 2/21 (9.5) vs 3/10 (30) | −17.3 (−46.4 to 6.7) |
| Overall responseg : 15/21 (71.4) vs 7/10 (70.0) | −7.3 (−27.5 to 21.4) | ||||||||
| Clinical response 28 days: 15/21 (71.4) vs 4/10 (40.0) | 31.4 (1.3 to 51.5) | ||||||||
| Microbiol response 5−9 days after EOT (cUTI): 8/11 (72.7) vs 5/5 (100) | −27.4 (−52.8 to 12.8) | ||||||||
| Sims 2017 (225) | Imi | 2 | RCT, NI | 302 (3 arms: high dose, low dose, control)h | cUTI | No | E. coli, 62%; K. pneumoniae, 15; MDR, 50.2% | Mortality: 0/99 vs 0/99 vs 0/100 | |
| Clinical response EOT: 69/71 (97.1) vs 78/79 (98.7) vs 79/80 (98.8) | High dose vs control: −1.6 (−8.9 to 4.2); low dose vs control: −0.0 (−5.8 to 5.6) | ||||||||
| Clinical response 5–9 days after EOT: 89.1% vs 91.8% vs 93.4% | High dose vs control: −4.4 (−15.2 to 5.3); low dose vs control: −1.6 (−11.2 to 7.5) | ||||||||
| Microbiol response 5–9 days after EOT: 61.5% vs 68.1% vs 70.4% | High dose vs control: −8.9 (−24.6 to 7.1); low dose vs control: −2.4 (−17.4 to 12.8) | ||||||||
| Lucasti 2016 (226) | Imi | 2 | RCT, NI | 351 (3 arms: high dose, low dose, control)h | cIAI | No | E. coli, 65%; K. pneumoniae, 14%; P. aeruginosa, 14%; Imi nonsusceptible, 13% | Mortality: 0/117 (0.0) vs 3/116 (2.6) vs 0/114 (0.0) | High dose vs control: 0.0 (−3.3 to 3.2); low dose vs control: 2.6 (−0.7 to 7.3) |
| Clinical response EOT: 80/89 (89.9) vs 88/96 (91.7) vs 83/92 (90.2) | High dose vs control: 0.3 (−9.6 to 8.9); low dose vs control: 1.4 (−7.2 to 10.3) | ||||||||
| Clinical response 5–9 days after EOT: 77/89 (86.5) vs 85/96 (88.5) vs 82/92 (89.1) | High dose vs control: −2.6 (−12.7 to 7.2); low dose vs control: −0.6 (−10.0 to 8.9) | ||||||||
| Microbiol response EOT: 81/83 (97.6) vs 86/86 (100) vs 82/84 (97.6) | High dose vs control: 0 (−6.3 to 6.2); low dose vs control: 2.4 (−2.0 to 8.3) | ||||||||
| Microbiol response 5–9 days after EOT: 76/78 (97.4) vs 80/82 (97.6) vs 78/80 (97.5) | High dose vs control: −0.1 (−6.7 to 6.4); low dose vs control: 0.1 (−6.3 to 6.5) | ||||||||
| NCT03293485 (229) | Single group | NAi | Nonrandomized | 83 Japanese p (cIAI 39, cUTI 44) | cIAI, cUTI | Immunosuppressive therapy, including high-dose corticosteroids | NS | Mortality: 1/81 (1.23) | |
| Clinical response TOC for cIAI: 28/34 (82.1) | |||||||||
| Microbiol response TOC for cUTI: 39/39 (100) | |||||||||
Imi, imipenem; Col, colistin.
NI, noninferiority.
I-R, imipenem-relebactam; cUTI, complicated urinary tract infection; cIAI, complicated intra-abdominal infection.
NP, nosocomial pneumonia.
Meror, meropenem resistant; MDR, multidrug resistant; NS, nonspecified.
EOT, end of therapy; TOC, test of cure; CI, confidence interval; microbiol, microbiological.
Definition of overall response: for hospital-acquired or ventilator-associated pneumonia, 28-day all-cause mortality: for cIAI, day 28 clinical response; and for cUTI, composite clinical and microbiologic response at end of follow-up. Favorable clinical response was defined as resolution of baseline signs and symptoms, and favorable microbiologic response was defined as eradication of baseline uropathogens. Death or missing data were considered treatment failures.
For the three arms: imipenem/cilastatin+relebactam 250 mg, imipenem/cilastatin+relebactam 125 mg, and imipenem/cilastatin alone, all administered four times daily.
NA, nonapplicable.