Zavicefta vs. Meropenem in Hospital-Acquired Pneumonia: REPROVE trial

Zavicefta is as effective as a carbapenem in hospitalised patients with aerobic Gram-negative HAP, including VAP1,2 

Reprove Phase III trial: 879 hospitalised adults with HAP/VAP

The first randomised controlled trial to show non-inferiority, compared with a carbapenem, of an antimicrobial therapy targeting Gram-negative pathogens in HAP/VAP

Patients with favourable clinical response at TOC (%)*

Baseline pathogens: predominantly K. pneumoniae and P. aeruginosa including some ceftazidime-resistant strains. 100 patients (28%) had > 1 ceftazidime-resistant isolate.

ZAVICEFTA has a safety and tolerability profile consistent with both cephalosporins and carbapenems1,3-5

  • In Phase III clinical trials, the adverse event profile of ZAVICEFTA was similar to that seen with either best available therapy, doripenem or meropenem1,3-5
  • The most common (>5%) AEs for ZAVICEFTA were positive Direct Coombs test, nausea and diarrhoea6
  • Nausea and diarrhoea were usually mild or moderate in intensity1,3-6

Footnotes:

*Non-inferiority was concluded if the lower limit of the 95% CI was greater than –12.5%.1

†cMITT population comprised patients with minimum disease criteria but excluded patients with only non-target pathogens.1

‡The clinically evaluable 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.1

Abbreviations:

AE, adverse event; CE, clinically evaluable; CI, confidence interval; cMITT, clinically modified intention-to-treat; HAP, hospital-acquired pneumonia; K. pneumoniae, Klebsiella pneumoniae; P. aeruginosa, Pseudomonas aeruginosa; TOC, test of cure; VAP, ventilator-associated pneumonia.

References:

1.Torres A, et al. Lancet Infect Dis 2018;18:285–95; 2. Torres A, et al. Open Forum Infect Dis 2019;6:ofz149; 3. Mazuski JE, et al. Clin Infect Dis 2016;62:1380–9;  4. Carmeli Y, et al. Lancet Infect Dis 2016;16:661–73; 5. Wagenlehner FM, et al. Clin Infect Dis 2016;63:754–62; 6. ZAVICEFTA. Summary of Product Characteristics

Prescribing Information
Meronem IV 1g – SPC 
Legal Category: POM.       Basic NHS Cost: 10 vial pack £206.28
Meronem IV 500mg – SPC 
Legal Category: POM.       Basic NHS Cost: 10 vial pack £103.14

 

Piperacillin/tazobactam
Tazocin 2 g/0.25 g Powder for Solution for Infusion – SPC
Legal category: POM.       Basic NHS cost: 1 vial pack £7.65 
Tazocin 4  g/0.5 g Powder for Solution for Infusion – SPC
Legal category: POM.       Basic NHS cost: 1 vial pack £15.17 
 
Tygacil 50 mg Powder for Solution for Infusion – SPC
Legal Category: POM.       Basic NHS Cost: 10 vial pack £323.10
 
ZAVICEFTA® 2 g/0.5 g Powder for Concentrate for Solution for Infusion – SPC
Legal category: POM.       Basic NHS price: 10 vial pack £857.00.

PP-ZVA-GBR-0861. June 2020