Información de la droga para CIPRO XR (ciprofloxacin* extended-release tablets) (Bayer HealthCare Pharmaceuticals Inc.): CLINICAL STUDIES

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  • Uncomplicated Urinary Tract Infections (acute cystitis)

    CIPRO XR was evaluated for the treatment of uncomplicated urinary tract infections (acute cystitis) in a randomized, double-blind, controlled clinical trial conducted in the US. This study compared CIPRO XR (500 mg once daily for three days) with ciprofloxacin immediate-release tablets (CIPRO® 250 mg BID for three days). Of the 905 patients enrolled, 452 were randomly assigned to the CIPRO XR treatment group and 453 were randomly assigned to the control group. The primary efficacy variable was bacteriologic eradication of the baseline organism(s) with no new infection or superinfection at test-of-cure (Day 4 -11 Post-therapy).

    The bacteriologic eradication and clinical success rates were similar between CIPRO XR and the control group. The eradication and clinical success rates and their corresponding 95% confidence intervals for the differences between rates (CIPRO XR minus control group) are given in the following table:

    CIPRO XR 500 mgQD x 3 DaysCIPRO 250 mgBID x 3 Days
    Randomized Patients452453
    Per Protocol PatientsThe presence of a pathogen at a level of ≥ 105 CFU/mL was required for microbiological evaluability criteria, except for S. saprophyticus (≥ 104 CFU/mL).199223
    Bacteriologic Eradication at TOC (n/N) n/N =patients with baseline organism(s) eradicated and no new infections or superinfections/ total number of patients188/199 (94.5%)209/223 (93.7%)
    CI [-3.5%, 5.1%]
    Bacteriologic Eradication(by organism) at TOC (n/N) n/N =patients with specified baseline organism eradicated/patients with specified baseline organism
    E. coli156/160 (97.5%)176/181 (97.2%)
    E. faecalis10/11 (90.9%)17/21 (81.0%)
    P. mirabilis11/12 (91.7%)7/7 (100%)
    S. saprophyticus6/7 (85.7%)9/9 (100%)
    Clinical Response at TOC (n/N) n/N = patients with clinical success /total number of patients189/199 (95.0%)204/223 (91.5%)
    CI [-1.1%, 8.1%]

    Complicated Urinary Tract Infections and Acute Uncomplicated Pyelonephritis

    CIPRO XR was evaluated for the treatment of complicated urinary tract infections (cUTI) and acute uncomplicated pyelonephritis (AUP) in a randomized, double-blind, controlled clinical trial conducted in the US and Canada. The study enrolled 1,042 patients (521 patients per treatment arm) and compared CIPRO XR (1000 mg once daily for 7 to 14 days) with immediate-release ciprofloxacin (500 mg BID for 7 to 14 days). The primary efficacy endpoint for this trial was bacteriologic eradication of the baseline organism(s) with no new infection or superinfection at 5 to 11 days post-therapy (test-of-cure or TOC) for the Per Protocol and Modified Intent-To-Treat (MITT) populations.

    The Per Protocol population was defined as patients with a diagnosis of cUTI or AUP, a causative organism(s) at baseline present at ≥ 105 CFU/mL, no inclusion criteria violation, a valid test-of-cure urine culture within the TOC window, an organism susceptible to study drug, no premature discontinuation or loss to follow-up, and compliance with the dosage regimen (among other criteria). More patients in the CIPRO XR arm than in the control arm were excluded from the Per Protocol population and this should be considered in the interpretation of the study results. Reasons for exclusion with the greatest discrepancy between the two arms were no valid test-of-cure urine culture, an organism resistant to the study drug, and premature discontinuation due to adverse events.

    An analysis of all patients with a causative organism(s) isolated at baseline and who received study medication, defined as the MITT population, included 342 patients in the CIPRO XR arm and 324 patients in the control arm. Patients with missing responses were counted as failures in this analysis. In the MITT analysis of cUTI patients, bacteriologic eradication was 160/271 (59.0%) versus 156/248 (62.9%) in CIPRO XR and control arm, respectively [97.5% CI* (-13.5%, 5.7%)]. Clinical cure was 184/271 (67.9%) for CIPRO XR and 182/248 (73.4%) for control arm, respectively [97.5% CI* (-14.4%, 3.5%)]. Bacterial eradication in the MITT analysis of patients with AUP at TOC was 47/71 (66.2%) and 58/76 (76.3%) for CIPRO XR and control arm, respectively [97.5% CI* (-26.8%, 6.5%)]. Clinical cure at TOC was 50/71 (70.4%) for CIPRO XR and 58/76 (76.3%) for the control arm [97.5% CI* (-22.0%, 10.4%)].

    * confidence interval of the difference in rates (CIPRO XR minus control).

    In the Per Protocol population, the differences between CIPRO XR and the control arm in bacteriologic eradication rates at the TOC visit were not consistent between AUP and cUTI patients. The bacteriologic eradication rate for cUTI patients was higher in the CIPRO XR arm than in the control arm. For AUP patients, the bacteriologic eradication rate was lower in the CIPRO XR arm than in the control arm. This inconsistency was not observed between the two treatment groups for clinical cure rates. Clinical cure rates were 96.1% (198/206) and 92.1% (211/229) for CIPRO XR and the control arm, respectively.

    The bacterial eradication and clinical cure rates by infection type for CIPRO XR and the control arm at the TOC visit and their corresponding 97.5% confidence intervals for the differences between rates (CIPRO XR minus control arm) are given below for the Per Protocol population analysis:

    CIPRO XR 1000 mg QDCIPRO 500 mg BID
    Randomized Patients521521
    Per Protocol PatientsPatients excluded from the Per Protocol population were primarily those with no causative organism(s) at baseline or no organism present at ≥ 105 CFU/mL at baseline, inclusion criteria violation, no valid test-of-cure urine culture within the TOC window, an organism resistant to study drug, premature discontinuation due to an adverse event, lost to follow-up, or non-compliance with dosage regimen (among other criteria).206229
    cUTI Patients
    Bacteriologic Eradication at TOC (n/N) n/N = patients with baseline organism(s) eradicated and no new infections or superinfections/total number of patients148/166 (89.2%)144/177 (81.4%)
    CI [-0.7%, 16.3%]
    Bacteriologic Eradication(by organism) at TOC (n/N) n/N = patients with specified baseline organism eradicated/patients with specified baseline organism
    E. coli91/94 (96.8%)90/92 (97.8%)
    K. pneumoniae20/21 (95.2%)19/23 (82.6%)
    E. faecalis17/17 (100%)14/21 (66.7%)
    P. mirabilis11/12 (91.6%)10/10 (100%)
    P. aeruginosa3/3 (100%)3/3 (100%)
    Clinical Cure at TOC (n/N) n/N = patients with clinical success /total number of patients159/166 (95.8%)161/177 (91.0%)
    CI [-1.1%, 10.8%]
    AUP Patients
    Bacteriologic Eradication at TOC (n/N)35/40 (87.5%)51/52 (98.1%)
    CI [-34.8%, 6.2%]
    Bacteriologic Eradication of E. coliat TOC (n/N)35/36 (97.2%)41/41 (100%)
    Clinical Cure at TOC (n/N)39/40 (97.5%)50/52 (96.2%)
    CI [-15.3%, 21.1%]
    Of the 166 cUTI patients treated with CIPRO XR, 148 (89%) had the causative organism(s) eradicated, 8 (5%) had persistence, 5 (3%) patients developed superinfections and 5 (3%) developed new infections. Of the 177 cUTI patients treated in the control arm, 144 (81%) had the causative organism(s) eradicated, 16 (9%) patients had persistence, 3 (2%) developed superinfections and 14 (8%) developed new infections. Of the 40 patients with AUP treated with CIPRO XR, 35 (87.5%) had the causative organism(s) eradicated, 2 (5%) patients had persistence and 3 (7.5%) developed new infections. Of the 5 CIPRO XR AUP patients without eradication at TOC, 4 were considered clinical cures and did not receive alternative antibiotic therapy. Of the 52 patients with AUP treated in the control arm, 51 (98%) had the causative organism(s) eradicated. One patient (2%) had persistence.

  • References:

    • NCCLS, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically-Sixth Edition. Approved Standard NCCLS Document M7-A6, Vol. 23, No. 2, NCCLS, Wayne, PA, January, 2003.
    • NCCLS, Performance Standards for Antimicrobial Disk Susceptibility Tests-Eighth Edition. Approved Standard NCCLS Document M2-A8, Vol. 23, No. 1, NCCLS, Wayne, PA, January, 2003.
  • Drug Information Provided by National Library of Medicine (NLM).
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