Trial of Combination Antifungal Therapy (Vori+Mica vs. Vori+Placebo) in Invasive Aspergillosis

A Phase II Randomized, Double Blind, Placebo-controlled, Trial of Combination Antifungal Therapy (Voriconazole Plus Micafungin vs. Voriconazole Plus Placebo Equivalent) in the Treatment of Invasive Aspergillosis (IA) in Patients With Hematological Cancer

The purpose of this study is to evaluate the therapeutic effectiveness of combination antifungal therapy (CAT) of voriconazole plus micafungin versus voriconazole plus placebo equivalent as primary therapy for invasive aspergillosis (IA) in patients with hematological cancer.

Study Overview

• Status: Withdrawn
• Conditions: Aspergillosis
• Intervention / Treatment: Drug: Voriconazole, micafungin

Detailed Description

Patients will receive either IV micafungin 100 mg or placebo equivalent daily. Intravenous (IV)Voriconazole will be administered at a loading dose of 6 mg/kg every 12 hours for the first 24 hours followed by a maintenance dose of 4 mg/kg every 12 hours. Patients may be switched to oral voriconazole 200 mg BID provided aspergillosis response is achieved and gastrointestinal functions are intact.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas
    • Little Rock, Arkansas, United States, 72205
      • UAMS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The patient or legally authorized representative has signed an informed consent/assent.

   Assent will be obtained as required by the UAMS IRB.

2. The patient has a diagnosis of proven or probable invasive aspergillosis and with positive Aspergillus GM index (≥0.5 ng/ml) provide the patient is not receiving antibiotics, such as piperacillin-tazobactam, that are known to cause false positive GMI
3. The patient is 18 years of age or older.

Exclusion Criteria:

1. The patient is being treated with an unlicensed investigational drug for aspergillosis.
2. The patient has been administered an antifungal agent (voriconazole, itraconazole, posaconazole, caspofungin, micafungin, anidulafungin, amphotericin B, or lipid formulation of amphotericin B) for > 7 days immediately prior to randomization for treatment of the Probable, or Proven invasive aspergillosis for which the patient is being enrolled.
3. Patient has invasive aspergillosis but with negative Aspergillus GM index.
4. The patient is pregnant or lactating. If the patient is female and of childbearing potential, the patient must have a negative pregnancy test and avoid becoming pregnant while receiving study drug. A pregnancy test should be performed within 14 days prior to the first dose of study drug.
5. The patient has alkaline phosphatase, ALT, AST or total bilirubin greater than five times the upper limit of normal.
6. The patient has hepatic cirrhosis.
7. Patients with creatinine > 3 will be enrolled only if able to receive oral voriconazole (specify oral loading dose is 6 mg/kg PO Q 12 hours for 24 hours) then oral maintenance 200 mg PO q 12 hours).
8. The patient is on artificial ventilation, and unlikely to be extubated within 24 hours of study entry.
9. The patient has a history of allergy, hypersensitivity, or any serious reaction to the azole or echinocandin class of antifungal agents.
10. The patient has previously enrolled into this study.
11. The patient has a concomitant medical condition, which in the opinion of the Investigator may create an unacceptable additional risk.
12. The patient has an active microbiologically-documented deep infection due to a non-Aspergillus mold.
13. The patient has a life expectancy of less than seven days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Voriconazole, Micafungin; Patients will receive either IV micafungin 100 mg or placebo equivalent daily. Intravenous (IV) Voriconazole will be administered at a loading dose of 6 mg/kg every 12 hours for the first 24 hours followed by a maintenance dose of 4 mg/kg every 12 hours. Patients may be switched to oral voriconazole 200 mg BID provided aspergillosis response is achieved and gastrointestinal functions are intact.	Drug: Voriconazole, micafungin; Patients will receive either IV micafungin 100 mg or placebo equivalent daily. Intravenous (IV)Voriconazole will be administered at a loading dose of 6 mg/kg every 12 hours for the first 24 hours followed by a maintenance dose of 4 mg/kg every 12 hours. Patients may be switched to oral voriconazole 200 mg BID provided aspergillosis response is achieved and gastrointestinal functions are intact.
No Intervention: Voriconazole+Micafungin or Voriconazole+Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	Response is defined as normalization of the serum Aspergillus galactomannan index (GMI)values (first normal GMI value is considered day of response).	maximum 6 weeks

Collaborators and Investigators

• Sponsor: University of Arkansas
• Investigators: Study Chair: Elias Anaissie, MD, University of Arkansas

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: September 21, 2010
• First Submitted That Met QC Criteria: September 21, 2010
• First Posted (Estimate): September 22, 2010

Study Record Updates

• Last Update Posted (Estimate): April 20, 2012
• Last Update Submitted That Met QC Criteria: April 18, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Aspergillosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Micafungin; Voriconazole
• Other Study ID Numbers: UARK 2010-14