Effekt og sikkerhet

ZINPLAVA + CDI antibiotics: Superior to CDI antibiotics alone in reducing C difficile recurrence 1

Percentage of patients with CDI recurrence 3

ZINPLAVA + CDI antibiotics significantly reduced the CDI recurrence rate vs CDI antibiotics alone through 12 weeks following administration of study infusion (P<0.0001). 1

  • Pooled data from 2 large-scale clinical trials. 1
  • Compared ZINPLAVA + CDI antibiotics vs CDI antibiotics alone (n=1,554). 1
  • Efficacy end point: the proportion of patients with recurrence of CDI through 12 weeks following administration of the study infusion. 1
  • 39% of all study participants received 1 or more systemic antibiotics (during the 12-week follow-up period). 1

Study design: The efficacy of ZINPLAVA was investigated in 2 randomized, double-blind, placebo-controlled, multicenter, Phase 3 trials in 1,554 patients. All patients received concomitant SOC antibiotics for CDI. Adult patients had a confirmed diagnosis of CDI, which was defined as diarrhea (passage of ≥3 loose bowel movements as defined in the Bristol stool chart as types 5 through 7 in ≤24 hours) and a positive stool test for toxigenic C difficile from a stool sample collected ≤7 days before study entry. Patients received a 10- to 14-day course of oral SOC antibiotics for CDI (metronidazole, vancomycin, or fidaxomicin, chosen by the investigator). Patients on oral vancomycin or oral fidaxomicin could have also received IV metronidazole. A single infusion of ZINPLAVA or placebo was administered prior to completion of antibiotics, and patients were followed for 12 weeks following the infusion. The day of the infusion of ZINPLAVA or placebo ranged from before starting antibiotics up to day 14 of treatment, with a median on day 3. The efficacy end point was the proportion of patients with recurrence of CDI through 12 weeks following administration of the study infusion. 1

IV=intravenous; RRR=relative risk reduction; SOC=standard-of-care.

ZINPLAVA + CDI antibiotics reduced recurrence vs CDI antibiotics alone in certain prespecified high-risk patients 1

Immunocompromised patients 1

In the pooled studies, 21% of patients were immunocompromised (medical conditions or medications that may result in immunosuppression).

Severe CDI patients 1

In the pooled studies, 16% of patients presented with clinically severe CDI (Zar score ≥2 a).

Age ≥ 65 years 1

In the pooled studies, 51% of patients were ≥ 65 years of age.

History of CDI 1

In the pooled studies, 28% of patients had a history of CDI within the 6 months prior to the episode under treatment.

  • Patients infected with a hypervirulent strain (027, 078, or 244 ribotypes) who received CDI antibiotics alone had a 32.2% (n=37/115) recurrence rate, while patients who received ZINPLAVA + CDI antibiotics had a 21.6% (n=22/102) recurrence rate (95% CI, -10.6 [-22.1, 1.3]).
  • Patients infected with 027 ribotype who received CDI antibiotics alone had a 34.0% (n=34/100) recurrence rate, while patients who received ZINPLAVA + CDI antibiotics had a 23.6% (n=21/89) recurrence rate (95% CI, -10.4 [-23.0, 2.6]).

a Zar severity assessment score for C difficile. Variables included aged >60 years, 1 point; albumin <2.5 mg/dL, 1 point; temperature >101°F, 1 point; white blood cell count >15 x 109/L, 1 point; intensive care unit admission, 2 points; and pseudomembranous colitis on colonoscopy, 2 points. Zar score was assessed at randomization, after antibiotics were already initiated. 2

ZINPLAVA + CDI antibiotics reduced recurrence vs CDI antibiotics alone in certain prespecified high-risk patients 1

Percentage of immunocompromised patients with CDI recurrence 3

Percentage of severe CDI patients with CDI recurrence 3

Percentage of patients age ≥65 years with CDI recurrence 16

Percentage of patients with a history of CDI and CDI recurrence 3

ZINPLAVA: CDI-related hospital readmissions

  • In a post hoc analysis of readmissions in 1,050 hospitalized patients, ZINPLAVA reduced CDI-associated hospital readmissions, including inpatients at high risk for CDI recurrence. 3

Adapted from Prabhu V S, Cornely O A, Golan Y et al.

Referanser

  • 1.

    SPC Zinplava september 2017, avsnitt 4.1, 4.2, 4.8, 5.1.

  • 2.

    Zar FA, Bakkanagari SR, Moorthi KMLST, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302–307. doi:10.1086/519265.

  • 3.

    Prabhu V S, Cornely O A, Golan Y et al., Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment forClostridium difficileInfection, Clinical Infectious Diseases 2017;XX(00):1–4, DOI: 10.1093/cid/cix523

 
CD-00087 03/19