Table 5.
Open in new tab

Results from the two Phase II, prospective, randomized, double-blind comparative trials on ceftazidime/avibactam

StudyStudy populationStudy treatmentsEndpointsResults
efficacysafety and tolerability
Vazquez et al.43137 patientsCAZ/AVI 500/125 mg each iv q8h (n = 69) versus imipenem/cilastatin 500 mg/500 mg iv q6h (n = 68) for 7–14 days (step down to oral ciprofloxacin was permitted)
Inclusion criteriaPrimary endpoint

  • 18–90 years

Favourable microbiological response (FMR) at the test-of-cure (TOC) visit (5–9 days after the last dose of study drug)a19/27 (70.4%) CAZ/AVI arm
25/35 (71.4%) comparator arm
[observed difference −1.1% (95% CI:−27.2%–25%)]		AEb
46/68 (67.6%) CAZ/AVI arm
51/67 (76.1%) comparator arm

  • Acute pyelonephritis or other cUTI due to Gram-negative pathogens

Exclusion criteriaSecondary endpoint

  • Resistant uropathogen

FMR at the end of iv therapya25/26 (96.2%) CAZ/AVI arm
34/34 (100%) comparator arm		SAEc
6/68 (8.8%) CAZ/AVI arm
2/67 (3%) comparator arm

  • Antibiotic therapy within 48 h prior to the admission urine culture

FMR at the late follow-up (LFU) visit, 4–6 weeks post-therapya15/26 (57.7%) CAZ/AVI arm
18/30 (60%) comparator arm

  • Ileal loops

Clinical response at the end of iv therapyd28/28 (100%) CAZ/AVI arm
36/36 (100%) comparator arm

  • Vescicoureteral reflux

Clinical response at the TOC visitd24/28 (85.7%) CAZ/AVI arm
29/36 (80.5%) comparator arm

  • Complete obstruction of urinary tract

Clinical response at the LFU visitd21/28 (75%) CAZ/AVI arm
24/36 (66.7%) comparator arm

  • Perinephric or intrarenal abscess

  • Fungal UTI

  • Permanent indwelling catheter (nephrostomy)

  • Pregnant or breast-feeding women

  • History of hypersensitivity to study drug

Lucasti et al.44204 patients
Inclusion criteriaCAZ/AVI 2000/500 mg plus metronidazole 500 mg each iv q8h (n = 101) versus meropenem 1000 mg iv q8h (n = 102) for 5–14 daysClinical response at the TOC visita62/68 (91.2%) CAZ/AVI arm
71/76 (93.4%) comparator arm
 [estimated difference −2.2% (95% CI:−20.4%– 12.2%)]		AEe
65/101 (64.4%) CAZ/AVI arm
59/102 (57.8%) comparator arm

  • 18–90 years

  • cIAI requiring surgical intervention and antibiotics, due to Gram-negative pathogens

Exclusion criteria

  • Abdominal wall abscess

  • Small bowel obstruction or ischaemic bowel without perforation

  • Antibiotic therapy within 72 h of study therapy

  • Concurrent infections

  • Perinephric infections

  • Female genital tract infections

  • Infections due to pathogens resistant to study drugs

  • Sepsis or shock unresponsive to iv fluid challenge

Clinical response at the end of iv therapya66/68 (97.1%) CAZ/AVI arm
74/76 (97.4%) comparator arm
 [observed difference −0.3% (95% CI:−17.7%–15.4%)]		SAEf
9/101 (8.9%) CAZ/AVI arm
11/102 (10.8%) comparator arm

  • APACHE II score >25

  • Abnormal liver function

  • Chronic hepatitis or cirrhosis

  • Abnormal renal function (CLCR <50 mL/min)

  • Immunocompromised status

  • BMI >45 kg/m2

  • Haemoglobin levels <10 mg/dL

  • Neutrophil count <1500 cells/mm3

  • Platelet count <100 000 cells/mm3

StudyStudy populationStudy treatmentsEndpointsResults
efficacysafety and tolerability
Vazquez et al.43137 patientsCAZ/AVI 500/125 mg each iv q8h (n = 69) versus imipenem/cilastatin 500 mg/500 mg iv q6h (n = 68) for 7–14 days (step down to oral ciprofloxacin was permitted)
Inclusion criteriaPrimary endpoint

  • 18–90 years

Favourable microbiological response (FMR) at the test-of-cure (TOC) visit (5–9 days after the last dose of study drug)a19/27 (70.4%) CAZ/AVI arm
25/35 (71.4%) comparator arm
[observed difference −1.1% (95% CI:−27.2%–25%)]		AEb
46/68 (67.6%) CAZ/AVI arm
51/67 (76.1%) comparator arm

  • Acute pyelonephritis or other cUTI due to Gram-negative pathogens

Exclusion criteriaSecondary endpoint

  • Resistant uropathogen

FMR at the end of iv therapya25/26 (96.2%) CAZ/AVI arm
34/34 (100%) comparator arm		SAEc
6/68 (8.8%) CAZ/AVI arm
2/67 (3%) comparator arm

  • Antibiotic therapy within 48 h prior to the admission urine culture

FMR at the late follow-up (LFU) visit, 4–6 weeks post-therapya15/26 (57.7%) CAZ/AVI arm
18/30 (60%) comparator arm

  • Ileal loops

Clinical response at the end of iv therapyd28/28 (100%) CAZ/AVI arm
36/36 (100%) comparator arm

  • Vescicoureteral reflux

Clinical response at the TOC visitd24/28 (85.7%) CAZ/AVI arm
29/36 (80.5%) comparator arm

  • Complete obstruction of urinary tract

Clinical response at the LFU visitd21/28 (75%) CAZ/AVI arm
24/36 (66.7%) comparator arm

  • Perinephric or intrarenal abscess

  • Fungal UTI

  • Permanent indwelling catheter (nephrostomy)

  • Pregnant or breast-feeding women

  • History of hypersensitivity to study drug

Lucasti et al.44204 patients
Inclusion criteriaCAZ/AVI 2000/500 mg plus metronidazole 500 mg each iv q8h (n = 101) versus meropenem 1000 mg iv q8h (n = 102) for 5–14 daysClinical response at the TOC visita62/68 (91.2%) CAZ/AVI arm
71/76 (93.4%) comparator arm
 [estimated difference −2.2% (95% CI:−20.4%– 12.2%)]		AEe
65/101 (64.4%) CAZ/AVI arm
59/102 (57.8%) comparator arm

  • 18–90 years

  • cIAI requiring surgical intervention and antibiotics, due to Gram-negative pathogens

Exclusion criteria

  • Abdominal wall abscess

  • Small bowel obstruction or ischaemic bowel without perforation

  • Antibiotic therapy within 72 h of study therapy

  • Concurrent infections

  • Perinephric infections

  • Female genital tract infections

  • Infections due to pathogens resistant to study drugs

  • Sepsis or shock unresponsive to iv fluid challenge

Clinical response at the end of iv therapya66/68 (97.1%) CAZ/AVI arm
74/76 (97.4%) comparator arm
 [observed difference −0.3% (95% CI:−17.7%–15.4%)]		SAEf
9/101 (8.9%) CAZ/AVI arm
11/102 (10.8%) comparator arm

  • APACHE II score >25

  • Abnormal liver function

  • Chronic hepatitis or cirrhosis

  • Abnormal renal function (CLCR <50 mL/min)

  • Immunocompromised status

  • BMI >45 kg/m2

  • Haemoglobin levels <10 mg/dL

  • Neutrophil count <1500 cells/mm3

  • Platelet count <100 000 cells/mm3

CAZ/AVI, ceftazidime/avibactam; cUTI, complicated urinary tract infections; cIAIs, complicated intra-abdominal infections; AE, adverse events; SAE, serious adverse events.

aIn microbiologically evaluable (ME) population.

bMost common adverse events: constipation, diarrhoea, abdominal pain, headache, anxiety and injection/infusion site reactions.

cThree serious adverse events (renal failure, diarrhoea and accidental overdose of CAZ/AVI) were considered to be drug related in the CAZ/AVI arm and one (increased creatinine levels) in the control arm.

dIn clinically evaluable (CE) population.

eMost common adverse events: nausea, vomiting, abdominal pain, pyrexia, increased transaminase levels.

fThree deaths in the CAZ/AVI group and two in the control group (none considered to be drug related).

Table 5.
Open in new tab

Results from the two Phase II, prospective, randomized, double-blind comparative trials on ceftazidime/avibactam

StudyStudy populationStudy treatmentsEndpointsResults
efficacysafety and tolerability
Vazquez et al.43137 patientsCAZ/AVI 500/125 mg each iv q8h (n = 69) versus imipenem/cilastatin 500 mg/500 mg iv q6h (n = 68) for 7–14 days (step down to oral ciprofloxacin was permitted)
Inclusion criteriaPrimary endpoint

  • 18–90 years

Favourable microbiological response (FMR) at the test-of-cure (TOC) visit (5–9 days after the last dose of study drug)a19/27 (70.4%) CAZ/AVI arm
25/35 (71.4%) comparator arm
[observed difference −1.1% (95% CI:−27.2%–25%)]		AEb
46/68 (67.6%) CAZ/AVI arm
51/67 (76.1%) comparator arm

  • Acute pyelonephritis or other cUTI due to Gram-negative pathogens

Exclusion criteriaSecondary endpoint

  • Resistant uropathogen

FMR at the end of iv therapya25/26 (96.2%) CAZ/AVI arm
34/34 (100%) comparator arm		SAEc
6/68 (8.8%) CAZ/AVI arm
2/67 (3%) comparator arm

  • Antibiotic therapy within 48 h prior to the admission urine culture

FMR at the late follow-up (LFU) visit, 4–6 weeks post-therapya15/26 (57.7%) CAZ/AVI arm
18/30 (60%) comparator arm

  • Ileal loops

Clinical response at the end of iv therapyd28/28 (100%) CAZ/AVI arm
36/36 (100%) comparator arm

  • Vescicoureteral reflux

Clinical response at the TOC visitd24/28 (85.7%) CAZ/AVI arm
29/36 (80.5%) comparator arm

  • Complete obstruction of urinary tract

Clinical response at the LFU visitd21/28 (75%) CAZ/AVI arm
24/36 (66.7%) comparator arm

  • Perinephric or intrarenal abscess

  • Fungal UTI

  • Permanent indwelling catheter (nephrostomy)

  • Pregnant or breast-feeding women

  • History of hypersensitivity to study drug

Lucasti et al.44204 patients
Inclusion criteriaCAZ/AVI 2000/500 mg plus metronidazole 500 mg each iv q8h (n = 101) versus meropenem 1000 mg iv q8h (n = 102) for 5–14 daysClinical response at the TOC visita62/68 (91.2%) CAZ/AVI arm
71/76 (93.4%) comparator arm
 [estimated difference −2.2% (95% CI:−20.4%– 12.2%)]		AEe
65/101 (64.4%) CAZ/AVI arm
59/102 (57.8%) comparator arm

  • 18–90 years

  • cIAI requiring surgical intervention and antibiotics, due to Gram-negative pathogens

Exclusion criteria

  • Abdominal wall abscess

  • Small bowel obstruction or ischaemic bowel without perforation

  • Antibiotic therapy within 72 h of study therapy

  • Concurrent infections

  • Perinephric infections

  • Female genital tract infections

  • Infections due to pathogens resistant to study drugs

  • Sepsis or shock unresponsive to iv fluid challenge

Clinical response at the end of iv therapya66/68 (97.1%) CAZ/AVI arm
74/76 (97.4%) comparator arm
 [observed difference −0.3% (95% CI:−17.7%–15.4%)]		SAEf
9/101 (8.9%) CAZ/AVI arm
11/102 (10.8%) comparator arm

  • APACHE II score >25

  • Abnormal liver function

  • Chronic hepatitis or cirrhosis

  • Abnormal renal function (CLCR <50 mL/min)

  • Immunocompromised status

  • BMI >45 kg/m2

  • Haemoglobin levels <10 mg/dL

  • Neutrophil count <1500 cells/mm3

  • Platelet count <100 000 cells/mm3

StudyStudy populationStudy treatmentsEndpointsResults
efficacysafety and tolerability
Vazquez et al.43137 patientsCAZ/AVI 500/125 mg each iv q8h (n = 69) versus imipenem/cilastatin 500 mg/500 mg iv q6h (n = 68) for 7–14 days (step down to oral ciprofloxacin was permitted)
Inclusion criteriaPrimary endpoint

  • 18–90 years

Favourable microbiological response (FMR) at the test-of-cure (TOC) visit (5–9 days after the last dose of study drug)a19/27 (70.4%) CAZ/AVI arm
25/35 (71.4%) comparator arm
[observed difference −1.1% (95% CI:−27.2%–25%)]		AEb
46/68 (67.6%) CAZ/AVI arm
51/67 (76.1%) comparator arm

  • Acute pyelonephritis or other cUTI due to Gram-negative pathogens

Exclusion criteriaSecondary endpoint

  • Resistant uropathogen

FMR at the end of iv therapya25/26 (96.2%) CAZ/AVI arm
34/34 (100%) comparator arm		SAEc
6/68 (8.8%) CAZ/AVI arm
2/67 (3%) comparator arm

  • Antibiotic therapy within 48 h prior to the admission urine culture

FMR at the late follow-up (LFU) visit, 4–6 weeks post-therapya15/26 (57.7%) CAZ/AVI arm
18/30 (60%) comparator arm

  • Ileal loops

Clinical response at the end of iv therapyd28/28 (100%) CAZ/AVI arm
36/36 (100%) comparator arm

  • Vescicoureteral reflux

Clinical response at the TOC visitd24/28 (85.7%) CAZ/AVI arm
29/36 (80.5%) comparator arm

  • Complete obstruction of urinary tract

Clinical response at the LFU visitd21/28 (75%) CAZ/AVI arm
24/36 (66.7%) comparator arm

  • Perinephric or intrarenal abscess

  • Fungal UTI

  • Permanent indwelling catheter (nephrostomy)

  • Pregnant or breast-feeding women

  • History of hypersensitivity to study drug

Lucasti et al.44204 patients
Inclusion criteriaCAZ/AVI 2000/500 mg plus metronidazole 500 mg each iv q8h (n = 101) versus meropenem 1000 mg iv q8h (n = 102) for 5–14 daysClinical response at the TOC visita62/68 (91.2%) CAZ/AVI arm
71/76 (93.4%) comparator arm
 [estimated difference −2.2% (95% CI:−20.4%– 12.2%)]		AEe
65/101 (64.4%) CAZ/AVI arm
59/102 (57.8%) comparator arm

  • 18–90 years

  • cIAI requiring surgical intervention and antibiotics, due to Gram-negative pathogens

Exclusion criteria

  • Abdominal wall abscess

  • Small bowel obstruction or ischaemic bowel without perforation

  • Antibiotic therapy within 72 h of study therapy

  • Concurrent infections

  • Perinephric infections

  • Female genital tract infections

  • Infections due to pathogens resistant to study drugs

  • Sepsis or shock unresponsive to iv fluid challenge

Clinical response at the end of iv therapya66/68 (97.1%) CAZ/AVI arm
74/76 (97.4%) comparator arm
 [observed difference −0.3% (95% CI:−17.7%–15.4%)]		SAEf
9/101 (8.9%) CAZ/AVI arm
11/102 (10.8%) comparator arm

  • APACHE II score >25

  • Abnormal liver function

  • Chronic hepatitis or cirrhosis

  • Abnormal renal function (CLCR <50 mL/min)

  • Immunocompromised status

  • BMI >45 kg/m2

  • Haemoglobin levels <10 mg/dL

  • Neutrophil count <1500 cells/mm3

  • Platelet count <100 000 cells/mm3

CAZ/AVI, ceftazidime/avibactam; cUTI, complicated urinary tract infections; cIAIs, complicated intra-abdominal infections; AE, adverse events; SAE, serious adverse events.

aIn microbiologically evaluable (ME) population.

bMost common adverse events: constipation, diarrhoea, abdominal pain, headache, anxiety and injection/infusion site reactions.

cThree serious adverse events (renal failure, diarrhoea and accidental overdose of CAZ/AVI) were considered to be drug related in the CAZ/AVI arm and one (increased creatinine levels) in the control arm.

dIn clinically evaluable (CE) population.

eMost common adverse events: nausea, vomiting, abdominal pain, pyrexia, increased transaminase levels.

fThree deaths in the CAZ/AVI group and two in the control group (none considered to be drug related).

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