[Clinical Efficacy – REPRISE & REPROVE Page] | Rwanda

REPRISE & REPROVE

RECAPTURE

RECLAIM

BACTERAEMIA DATA

Ceftazidime/Avibactam Pfizer (ceftazidime and avibactam) has proven clinical efficacy across four Phase III international, randomised, noninferiority trials in 1423 adult patients with HAP/VAP, cIAI* or cUTI^1–4

REPRISE

In the REPRISE Phase III trial, Ceftazidime/Avibactam Pfizer was as effective as best available therapy in patients with cUTI or cIAI caused by Gram-negative pathogens¹

Adapted from Carmeli Y, et al. Lancet Infect Dis. 2016.

Baseline pathogens¹

Ceftazidime-resistant Enterobacterales (most commonly E. coli or K. pneumoniae) and P. aeruginosa

REPROVE

In the REPROVE Phase III trial, Ceftazidime/Avibactam Pfizer was as effective as a carbapenem in patients with HAP/VAP caused by Gram-negative pathogens²

*Ceftazidime/Avibactam Pfizer is as effective as a carbapenem when combined with metronidazole in hospitalised patients with Gram-negative cIAIs.⁴
†Formal statistical comparison not performed; corresponding CIs for the efficacy of best available therapy were used to provide context for descriptive estimates of ceftazidime and avibactam efficacy.¹
‡Patients in the mMITT population included all patients who had a diagnosis of cUTI or cIAI with at least one ceftazidime-resistant Gram-negative pathogen, as confirmed by the central laboratory, and who received at least one dose of study drug.¹
§Preferred best available therapy options for cUTI and cIAI were 5–21 days of treatment with meropenem, imipenem, doripenem, colistin and (for cIAI) tigecycline, administered intravenously, but any therapy, including combination treatment, was permitted.¹

||Non-inferiority was concluded if the lower limit of the 95% CI was greater than -12.5%.²
¶cMITT population comprised patients with minimum disease criteria but excluded patients with only non-target pathogens.²
**The CE population comprised patients in the cMITT population who received an adequate course of treatment and had an assessable clinical outcome within the assessment window, no protocol deviations that could affect the assessment of efficacy, and no unacceptable previous or concomitant antibiotics.²

CE, clinically evaluable; CI, confidence interval; cIAI, complicated intra-abdominal infection; cMITT, clinically modified intention-to-treat; cUTI, complicated urinary tract infection; HAP, hospital-acquired pneumonia; LTO, limited treatment options; mMITT, microbiologically modified intent-to-treat; TOC, test of cure;
VAP, ventilator-associated pneumonia.

References

1. Carmeli Y, Armstrong J, Laud PJ, et al. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis. 2016;16:661–673. 2. Torres A, Zhong N, Pach J, et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018;18:285–295. 3. Wagenlehner FM, Sobel JD, Newell P, et al. Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect Dis. 2016;63:754–762. 4. Mazuski JE, Gasink LB, Armstrong J, et al. Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program. Clin Infect Dis. 2016;62:1380–1389.

In the RECAPTURE Phase III trial, Ceftazidime/Avibactam Pfizer was as effective as a carbapenem in patients with cUTI caused by Gram-negative pathogens³

Baseline pathogens³

Predominantly E. coli and K. pneumoniae including some ceftazidime-resistant strains

*Ceftazidime/Avibactam Pfizer is as effective as a carbapenem when combined with metronidazole in hospitalised patients with Gram-negative cIAIs.⁴
†Non-inferiority was concluded if the lower limit of the 95% CI was greater than -12.5%.³
‡The mMITT population comprised all randomised patients with minimum disease criteria and eligible baseline pathogen(s).³

CI, confidence interval; cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; HAP, hospital-acquired pneumonia; LTO, limited treatment options; mMITT, microbiologically modified intent-to-treat; TOC, test of cure; VAP, ventilator-associated pneumonia.

References:

In the RECLAIM Phase III trial, Ceftazidime/Avibactam Pfizerwas as effective as a carbapenem when combined with metronidazole in patients with cIAI caused by Gram-negative pathogens⁴

Adapted from Mazuski JE, et al. Clin Infect Dis. 2016.

Baseline pathogens⁴

E. coli, K. pneumoniae and P. aeruginosa including some ceftazidime-resistant strains.
417 patients (40%) had polymicrobial infection at baseline.

*Ceftazidime/Avibactam Pfizer is as effective as a carbapenem when combined with metronidazole in hospitalised patients with Gram-negative cIAIs.⁴
†Non-inferiority was considered met if the lower limit of the 95% CI for between-group difference was greater than the prespecified non-inferiority margin of -12.5%.⁴
‡Patients in the MITT population are defined as patients who received study drug and met the clinical disease criteria.⁴

CI, confidence interval; cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; HAP, hospital-acquired pneumonia; LTO, limited treatment options; MITT, modified intent-to-treat; TOC, test of cure; VAP, ventilator-associated pneumonia.

References:

The efficacy of Ceftazidime/Avibactam Pfizer(ceftazidime and avibactam) for the treatment of adult patients with bacteraemia associated with HAP/VAP, cIAI or cUTI is supported by data from a subset of 101 adult patients across the Phase III clinical trial programme^1–3*

Adapted from Mazuski JE, et al. ECCMID. 2020

In this post-hoc analysis,^§ Ceftazidime/Avibactam Pfizer showed favourable clinical and microbiological response rates in adult patients with bacteraemiaǁ associated with HAP/VAP, cIAI or cUTI^2,3

Baseline pathogens²

E. coli (69%); K. pneumoniae (21%); P. aeruginosa (17%).

Primary dianoses²

Acute pyelonephritis (47%); VAP (15%).

*Five Phase III international, randomised, non-inferiority trials in patients with HAP/VAP, cIAI or cUTI.^1-3
†Meropenem in HAP/VAP and cIAI; doripenem in cUTI.³
‡Ceftazidime/Avibactam Pfizer plus metronidazole for cIAI.³
§Exploratory analysis of adult patients with Gram-negative bacteraemia.²
ǁDefined as any patient with ≥1 bacteria identified from a blood culture at baseline for all studies, except for RECAPTURE, which also required the same pathogen to be identified in a urine sample at >105 CFUs/mL.³

CFU, colony-forming unit; CI, confidence interval; cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; HAP, hospital-acquired pneumonia; LTO, limited treatment options; TOC, test of cure; VAP, ventilator-associated pneumonia.

References:
1. Ceftazidime/Avibactam Pfizer [SmPC], Italy, Verona: Pfizer; Feb 2021. ; 2. Mazuski JE, et al. ECCMID 2020; abstract 985; 3. European Medicines Agency. CHMP extension of indication variation assessment report for Ceftazidime/Avibactam Pfizer. EMA/CHMP/302938/2020.