TABLE 1.
Clinical studies.
| ClinicalTrials.gov ID, status, locations | Study design | No of patients in mITT | Dosing regiment | Primary outcome | Secondary outcome | Interpretation | Ref | ||
|---|---|---|---|---|---|---|---|---|---|
| Phase II trials | |||||||||
| APEKS-cUTI NCT02321800, Completed, United States, Belgium, Canada, Czechia, Estonia, France, Georgia, Germany, Hungary, Japan, Russian Federation, Serbia, Spain, Taiwan, Ukraine | Treatment of cUTI with or without pyelonephritis or AUP | FDC: 252 | 2 g (t′ 1 h) q8 h 7–14 days | Composite of clinical response and microbiological response at TOC in the mITT population [% (n/N)] | Microbiological response per patient at EA/EOT/TOC/FUP (%) | FDC was superior to high dose IPM/CIS. Cefiderocol is safe and effective for the treatment of cUTI. |
ClinicalTrials.gov (2014); Portsmouth et al. (2018) | ||
| FDC: IPM/CIS: |
92.1/96.8/73.0/57.1 90.8/95.8/56.3/43.7 |
||||||||
| IPM/CIS: 119 | 1 g/1 g (t′ 1 h) q8 7–14 days | FDC: 72.6 (183/252) | Microbiological response per pathogen at EA/EOT/TOC/FUP (%) | ||||||
| IPM/CIS: 54.6 (65/119) | |||||||||
| Multicenter, double-blind, parallel-group non-inferiority trial | |||||||||
| E. coli (152, 79) | |||||||||
| Total: 371 | FDC: | 92.8/98.7/75.0/59.9 | |||||||
| IPM/CIS: | 94.9/97.5/58.2/41.8 | ||||||||
| K. pneumoniae (48, 25) | |||||||||
| FDC: | 89.6/97.9/75.0/58.3 | ||||||||
| IPM/CIS: | 88.0/92.0/52.0/52.0 | ||||||||
| P. eruginosa (18, 5) | |||||||||
| FDC: | 94.4/88.9/44.4/27.8 | ||||||||
| IPM/CIS: | 80.0/100/60.0/20.0 | ||||||||
| P. mirabilis (17, 2) | |||||||||
| FDC: | 88.2/94.1/76.5/64.7 | ||||||||
| IPM/CIS: | 100/100/50.0/0 | ||||||||
| Clinical response per patient at EA/EOT/TOC/FUP (%) | |||||||||
| FDC: | 90.5/98.0/89.7/81.3 | ||||||||
| IPM/CIS: | 90.8/99.2/87.4/72.3 | ||||||||
| Clinical response per pathogen (%) | |||||||||
| E. coli (146, 77) | |||||||||
| FDC: | 91.8/97.9/89.7/82.9 | ||||||||
| IPM/CIS: | 96.1/98.7/88.3/72.7 | ||||||||
| K. pneumoniae (46, 25) | |||||||||
| FDC: | 82.6/100/89.1/82.6 | ||||||||
| IPM/CIS: | 88.0/100/84.0/68.0 | ||||||||
| P. eruginosa (15, 4) | |||||||||
| FDC: | 93.3/93.3/73.3/53.3 | ||||||||
| IPM/CIS: | 75.0/100/75.0/75.0 | ||||||||
| P. mirabilis (13, 1) | |||||||||
| FDC: | 84.6/100/100/84.6 | ||||||||
| IPM/CIS: | 100/100/100/100 | ||||||||
| GAMECHANGERNCT03869437, In progress, Australia, Greece, Italy, Singapore, Thailand, Turkey | Treatment of BSI | FDC | 2 g (t′ 3 h) q8 h 14 days | All-cause mortality at day 14 | Health (2018); ClinicalTrials.gov (2019) | ||||
| Multicenter, randomized, open-label trial | BAT Total 284 |
Chosen by the investigator 14 days |
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| Phase III trials | |||||||||
| CREDIBLE-CR NCT02714595, Completed, United States, Brazil, Croatia, France, Germany, Greece, Guatemala, Israel, Italy, Japan, Korea, Thailand, Turkey, United Kingdom | Treatment of HAP, VAP, HCAP, cUTI or BSI/sepsis | FDC: 80 | 2 g (t′ 3 h) q8 h 7–14 days | Clinical outcome per patient at TOC for HAP/VAP/HCAP, BSI/sepsis, cUTI | All-cause mortality at day 14, day 28 and day 49 % Day 14, Day 28/Day 49 |
Microbiological eradiation in cUTI subgroup was higher in FDC group than BAT group Higher mortality rates were detected in the FDC group than in the BAT group for HAP/VAP/HCAP and BSI/sepsis subgroups |
FDA (2019a) | ||
| Clinical cure (% (n/N)) | |||||||||
| Multicenter randomized, open-label | BAT: 38 Total 118 |
Chosen by the investigator 7–14 days | Overall | Overall | |||||
| FDC: | 52.5 (42/80) | FDC: | 18.8/24.8/33.7 | ||||||
| BAT: | 50.0 (19/38) | BAT: | 12.2/18.4/20.4 | ||||||
| HAP/VAP/HCAP | HAP/VAP/HCAP | ||||||||
| FDC: | 50.0 (20/40) | FDC: | 24.4/31.1/42.2 | ||||||
| BAT: | 52.6 (10/19) | BAT: | 13.6/18.2/18.2 | ||||||
| BSI/sepsis | BSI/sepsis | ||||||||
| FDC: | 43.5 (10/23) | FDC: | 16.7/23.3/36.7 | ||||||
| BAT: | 2.9 (46/14) | BAT: | 5.9/17.6/23.5 | ||||||
| cUTI | cUTI | ||||||||
| FDC: | 70.6 (12/17) | FDC: | 11.5/15.4/15.4 | ||||||
| BAT: | 60.0 (3/5) | BAT: | 20/20/20: | ||||||
| Microbiological outcome per patient at TOC for cUTI, HAP/VAP/HCAP, BSI/sepsis Eradication (% (n/N)) |
All-cause mortality at day 49 by baseline pathogen [% (n/N)] | ||||||||
| cUTI | A. baumannii | ||||||||
| FDC: | 52.9 (9/17) | FDC: | 48.7 (19/39) | ||||||
| BAT: | 20.0 (1/5) | BAT: | 23.5 (4/17)) | ||||||
| Overall | K. pneumoniae | ||||||||
| FDC: | 31.3 (25/80) | FDC: | 23.5 (8/34) | ||||||
| BAT: | 23.7 (9/38) | BAT: | 25.0 (4/16) | ||||||
| HAP/VAP/HCAP | P. eruginosa | ||||||||
| FDC: | 22.5 (9/40) | FDC: | 35.3 (6/17) | ||||||
| BAT: | 21.1 (4/19 | BAT: | 16.7 (2/12) | ||||||
| BSI/sepsis | S. maltophilia | ||||||||
| FDC: | 30.4 (7/23) | FDC: | 80.0 (4/5) | ||||||
| BAT: | 28.6 (4/14) | BAT: | 0.0 (0/0) | ||||||
| APEKS-NPNCT03032380, Completed, United States, Belgium, Canada, Czechia, Estonia, France, Georgia, Germany, Israel, Japan, Latvia, Philippines, Puerto Rico, Russian Federation, Serbia, Spain, Taiwan, Ukraine | Treatment of nosocomial pneumonia, including HAP, VAP and HCAP Multicenter, randomized, double-blind parallel-group |
FDC 148 | 2 g (t′ 3 h) q8 h 7–14 days | All-cause mortality at day 14% (nN) | Clinical outcome at TOC Clinical cure % | FDC was non-inferior to high dose MEM. | Health (2018); Wunderink et al. (2019) | ||
| MEM 150 | 2 g (t′ 3 h) q8 h 7–14 days | Day 14 FDC: MEM: Day 28 FDC: MEM: |
Day 28 12.4 (18/145)11.6 (17/146)21.020.5 | FDC: MEM: Microbiological eradication at TOC % FDC: MEM: |
64.8 66.7 7.6 48 |
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| LZD in each group 600 mg (t′ 30 min–2 h) q12 h ≥5 days |
Mcrobiologically evaluable per protocol population FDC: MEM: |
13.0 (13/100) | Clinical cure rates per pathogens at TOC K. pneumoniae FDC: MEM: E. coli |
64.6 (31/48) 65.9 (29/44) |
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| Total: 298 | FDC: | 63.2 (12/19) | |||||||
| MEM: | 59.1 (13/22) | ||||||||
| P. eruginosa | |||||||||
| FDC: | 66.7 (16/24) | ||||||||
| MEM: | 70.8 (17/24) | ||||||||
|
A. baumannii
FDC: MEM: |
52.2 (12/23) 58.3 (14/24) |
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UTI, complicated urinary tract infection; AUP, uncomplicated pyelonephritis; HAP, hospital acquired pneumonia; VAP, ventilator associated pneumonia; HCAP, healthcare-associated pneumonia; BSI, bloodstream infections; FDC, cefiderocol; IPM/CIS, imipenem/cilastatin; MEM, meropenem; LZD, linezolid; BAT, best available therapy; EA, early assessment; EOT, end of treatment; TOC, time of cure; FUP, follow-up; mITT, modified intention-to-treat.