Anidulafungin Plus Voriconazole Versus Voriconazole For The Treatment Of Invasive Aspergillosis - Full Text View

Purpose

This study compares the effectiveness and safety of the combination of anidulafungin and voriconazole compared to that of voriconazole alone (which is generally considered the standard of care) for the treatment of Invasive Aspergillosis.

Condition	Intervention	Phase
Aspergillosis	Drug: voriconazole Drug: anidulafungin	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Prospective, Randomized Trial Comparing The Efficacy Of Anidulafungin And Voriconazole In Combination To That Of Voriconazole Alone When Used For Primary Therapy Of Proven Or Probable Invasive Aspergillosis

Resource links provided by NLM:

MedlinePlus related topics: Aspergillosis

Drug Information available for: Voriconazole Anidulafungin

Genetic and Rare Diseases Information Center resources: Aspergillosis

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

All-cause Mortality at Week 6 in Participants With Proven or Probable Invasive Aspergillosis [ Time Frame: Day 1 to Day 42 (Week 6) ]
Number of deaths measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.

Secondary Outcome Measures:

Global Response at Week 6 [ Time Frame: Baseline, Day 42 (Week 6) ]
Number of participants with a successful response (complete or partial global response). Complete response = resolution of all clinical signs and symptoms and >90% of lesions due to IA that were visible on radiologic studies at baseline (BL); partial response = clinical improvement and >50% improvement in radiological findings present at BL.
All-cause Mortality at Week 6 in Participants With Possible, Probable, or Proven Invasive Aspergillosis (IA) [ Time Frame: Day 1 to Day 42 (Week 6) ]
Number of deaths due to any cause measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
All-cause Mortality at Week 12 in Participants With Probable or Proven Invasive Aspergillosis (IA) [ Time Frame: Day 1 to Day 84 (Week 12) ]
Number of deaths due to any cause measured 12 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
Mortality Due to Invasive Aspergillosis (IA) at Week 6 in Participants With Probable or Proven IA [ Time Frame: Day 1 to Day 42 (Week 6) ]
Number of deaths due to Invasive Aspergillosis measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
Time to Death: All-Cause Mortality [ Time Frame: Day 1 to Day 84 (Week 12) ]
Survival time from start of treatment. Time to death defined as date of death due to any cause minus first treatment date + 1.
Time to Death Due to Invasive Aspergillosis (IA) [ Time Frame: Day 1 to Day 84 (Week 12) ]
Survival time from start of treatment. Time to death defined as date of death due to IA minus first treatment date + 1.


Enrollment:	459
Study Start Date:	July 2008
Study Completion Date:	May 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Voriconazole Voriconazole monotherapy	Drug: voriconazole First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV BID plus anidulafungin placebo IV qd. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin placebo IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin placebo IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Other Name: Vfend
Experimental: Voriconazole and Anidulafungin Combination therapy with voriconazole and anidulafungin	Drug: anidulafungin First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Other Name: Eraxis Drug: voriconazole First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Other Name: Vfend

Arms

Assigned Interventions

Active Comparator: Voriconazole

Voriconazole monotherapy

Drug: voriconazole

First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV BID plus anidulafungin placebo IV qd.

Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin placebo IV qd.

Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin placebo IV qd,

OR

Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.

Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.

Other Name: Vfend

Experimental: Voriconazole and Anidulafungin

Combination therapy with voriconazole and anidulafungin

Drug: anidulafungin

First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter.

Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd.

Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd,

OR

Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.

Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.

Other Name: Eraxis

Drug: voriconazole

First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter.

Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd.

Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd,

OR

Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.

Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.

Other Name: Vfend

Eligibility


Ages Eligible for Study:	16 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Immunocompromised state due to either 1. receipt of hematopoeitic stem cell transplantation or 2. hematologic malignancy;
Diagnosis of possible, probable, or proven invasive aspergillosis.

Exclusion Criteria:

Patients with aspergilloma or chronic aspergillosis
Receipt of 4 or more days of systemic antifungal treatment for the current episode of invasive aspergillosis
Anticipated survival of less than 5 days or Karnofsky score <=20

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00531479

Show 107 Study Locations

Sponsors and Collaborators

Pfizer

Investigators


Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Marr KA, Schlamm HT, Herbrecht R, Rottinghaus ST, Bow EJ, Cornely OA, Heinz WJ, Jagannatha S, Koh LP, Kontoyiannis DP, Lee DG, Nucci M, Pappas PG, Slavin MA, Queiroz-Telles F, Selleslag D, Walsh TJ, Wingard JR, Maertens JA. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015 Jan 20;162(2):81-9. doi: 10.7326/M13-2508. Erratum in: Ann Intern Med. 2015 Mar 17;162(6):463.

Liu P, Mould DR. Population pharmacokinetic-pharmacodynamic analysis of voriconazole and anidulafungin in adult patients with invasive aspergillosis. Antimicrob Agents Chemother. 2014 Aug;58(8):4727-36. doi: 10.1128/AAC.02809-13. Epub 2014 Jun 9.

Liu P, Mould DR. Population pharmacokinetic analysis of voriconazole and anidulafungin in adult patients with invasive aspergillosis. Antimicrob Agents Chemother. 2014 Aug;58(8):4718-26. doi: 10.1128/AAC.02808-13. Epub 2014 Jun 9.


Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00531479 History of Changes
Other Study ID Numbers:	A8851009
Study First Received:	September 14, 2007
Results First Received:	April 3, 2012
Last Updated:	April 3, 2012

Additional relevant MeSH terms:


Aspergillosis Hyalohyphomycosis Dermatomycoses Skin Diseases, Infectious Infection Mycoses Skin Diseases Voriconazole Anidulafungin Echinocandins Antifungal Agents	Anti-Infective Agents 14-alpha Demethylase Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Steroid Synthesis Inhibitors Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Cytochrome P-450 CYP3A Inhibitors

ClinicalTrials.gov processed this record on June 23, 2017