Dataset Information

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials.

ABSTRACT: To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non- albicans Candida species.Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200?mg on day 1, followed by 100?mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5-10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ?14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population.In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%-80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin.These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population.

SUBMITTER: Kullberg BJ

PROVIDER: S-EPMC5890675 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials.

Kullberg Bart Jan BJ Vasquez José J Mootsikapun Piroon P Nucci Marcio M Paiva José-Artur JA Garbino Jorge J Yan Jean Li JL Aram Jalal J Capparella Maria Rita MR Conte Umberto U Schlamm Haran H Swanson Robert R Herbrecht Raoul R

The Journal of antimicrobial chemotherapy 20170801 8

<h4>Objectives</h4>To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non- albicans Candida species.<h4>Methods</h4>Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (c ...[more]

PMID: 28459966

Similar Datasets

Project description:The incidence of nosocomial invasive fungal infections involving Candida spp. has increased markedly in recent years in patients undergoing abdominal surgery. This post hoc analysis aimed to determine the efficacy and safety of anidulafungin treatment in patients with intra-abdominal candidiasis (IAC) from five prospective studies (one comparative and four open-label) of adult surgical patients with microbiologically confirmed Candida intra-abdominal infection. Patients received an intravenous (IV) loading dose of anidulafungin 200 mg, followed by a daily 100-mg maintenance dose. Per study protocols, some patients could be switched to an oral azole after ??5 or ??10 days of IV treatment. Antifungal treatment was maintained for ??14 days after the last positive Candida culture and resolution of symptoms. The global response rate (GRR) at the end of IV treatment (EOIVT) was the primary endpoint. GRR at the end of therapy (EOT), all-cause mortality at days 14 and 28, and safety was also evaluated. Seventy-nine patients had IAC from peritoneal fluid or hepatobiliary tract. C. albicans (72.2%) and C. glabrata (32.9%) were the most common pathogens. Overall GRR was 73.4% and 67.1% at EOIVT and EOT, respectively. All-cause mortality was 17.7% at day 14 and 24.1% at day 28 in the modified intent-to-treat population. Anidulafungin was well tolerated in this population, with most adverse events mild or moderate in severity. In these patients with IAC, anidulafungin showed a GRR at EOIVT similar to the anidulafungin registrational trial, and the results of our analysis confirmed the known safety profile of anidulafungin. ClinicalTrials.gov registration number NCT00496197, registered July 3, 2007, https://clinicaltrials.gov/ct2/show/study/NCT00496197 ; ClinicalTrials.gov registration number NCT00548262, registered October 19, 2007, https://clinicaltrials.gov/ct2/show/record/NCT00548262 ; ClinicalTrials.gov registration number NCT00537329, registered September 25, 2007, https://clinicaltrials.gov/ct2/show/record/NCT00537329 ; ClinicalTrials.gov registration number NCT00689338, registered May 29, 2008, https://clinicaltrials.gov/ct2/show/study/NCT00689338 ; ClinicalTrials.gov registration number NCT00805740, registered November 26, 2008, https://clinicaltrials.gov/ct2/show/NCT00805740.

Project description:During the past decade, the incidence of Candida infections in hospitalized patients has increased, with fluconazole being the most commonly prescribed systemic antifungal agent for these infections. However, the 2009 Infectious Diseases Society of America (IDSA) candidiasis guidelines recommend an echinocandin for the treatment of candidemia/invasive candidiasis in patients who are considered to be "moderately severe or severely" ill. To validate these guidelines, clinical trial data were reviewed.A secondary analysis of data from a previously published prospective, randomized, double-blind clinical trial was performed; it compared anidulafungin with fluconazole for the treatment of invasive candidiasis and candidemia. Patients with critical illness were identified at study entry by using the following criteria: Acute Physiology and Chronic Health Evaluation (APACHE) II score of ? 15, evidence of severe sepsis (sepsis and one or more end-organ dysfunctions) present, and/or patient was in intensive care. Global response rates were compared at the end of intravenous study treatment (the primary end point of the original study) and all-cause mortality at 14 and 28 days from study entry in this group.The patients (163 (66.5%) of 245) fulfilled at least one criterion for critical illness (anidulafungin, n = 89; fluconazole, n = 74). No significant differences were found in baseline characteristics between the two treatment groups. The global response rate was 70.8% for anidulafungin and 54.1% for fluconazole (P = 0.03; 95% confidence interval (CI): 2.0 to 31.5); all-cause mortality was 10.1% versus 20.3% at 14 days (P = 0.08; 95% CI, -0.9 to 21.3) and was 20.2% versus 24.3% at 28 days (P = 0.57; 95% CI, -8.8 to 17.0) for anidulafungin and fluconazole, respectively.In this post hoc analysis, anidulafungin was more effective than fluconazole for treatment of severely ill patients with candidemia, thus supporting the 2009 IDSA guidelines.Clinicaltrials.gov NCT00058682.

Project description:IntroductionAlthough the safety of celecoxib has been investigated, limited data are available on complications affecting the entire (upper and lower) gastrointestinal (GI) tract, with no patient-level pooled analyses of upper and lower GI outcomes available. We therefore evaluated the upper and lower GI safety of celecoxib by using patient-level data from randomized controlled trials (RCTs).MethodsThis patient-level pooled analysis included 52 prospective, randomized, double-blind parallel-group studies from the Celecoxib Clinical Database. Each study had a planned duration of continuous treatment with celecoxib or a nonselective nonsteroidal antiinflammatory drug (nsNSAID), rofecoxib, or the placebo comparator arm for at least 4 weeks. All studies with final reports completed by 1 October 2007 were included. The primary end point was the combined incidence of clinically significant upper and lower GI events (CSULGIEs). An independent blinded committee reviewed and adjudicated all end points by using predefined criteria and all available reported adverse events, laboratory data, and case narratives. All doses of celecoxib and all doses of all nsNSAIDs were pooled for analysis.ResultsThe pooled analysis involved 51,048 patients; 28,614 were randomized to celecoxib; 15,278 to nsNSAIDs (including 3,248 patients taking naproxen, 2,640 taking ibuprofen, 8,066 taking diclofenac, 1,234 taking loxoprofen, and 90 taking ketoprofen); 5,827 to placebo and 1,329 to rofecoxib. The mean age was 60 years, and 65% were women. Data on 1,042 patients with potential GI events were reviewed for end-points adjudication; the adjudication committee confirmed 89 patients with CSULGIEs. The majority were in the celecoxib and nsNSAID groups (with raw incidence proportions of 37 (0.1%) and 40 (0.3%), respectively). The incidence rates were 0.3, 0.9 and 0.3 per 100 patient-years in the celecoxib, nsNSAID, and placebo groups, respectively. The time to incidence of CSULGIEs was significantly longer with celecoxib than with nsNSAIDs (P=0.0004).ConclusionsWhen compared with nsNSAIDs, celecoxib is associated with a significantly lower risk of all clinically significant GI events throughout the entire GI tract. This pooled analysis of 52 RCTs significantly advances the understanding of the upper and lower GI safety profile of celecoxib and its potential benefits to patients.

Dataset Information

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials.

Publications

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure