Anidulafungin Versus Fluconazole for the Prevention of Fungal Infections in Liver Transplant Recipients

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Completed
• CT.gov ID: NCT00841971
• Collaborator: (none)
• Enrollment: 200
• Locations: 6
• Arms: 2
• Duration (Months): 50.9
• Patients Per Site: 33.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of anidulafungin versus fluconazole for the prevention of fungal diseases in liver transplant recipients

Condition or Disease	Intervention/Treatment	Phase
Mycoses; Fungemia; Central Nervous System Fungal Infections; Lung Diseases, Fungal	Drug: Anidulafungin; Drug: Fluconazole	Phase 4

Detailed Description

A number of well characterized risk factors have been shown to portend a high risk of opportunistic mycoses after liver transplantation.

Retransplantation and renal failure are amongst the most significant risk factors for invasive fungal infections in these patients.

Most Invasive fungal infections in these high-risk patients occur within the first month posttransplant.

Studies utilizing universal prophylaxis have primarily employed fluconazole. A recent meta-analysis of prophylactic trials documented a beneficial effect on morbidity and attributable mortality, but an emergence of infections due to non-albicans Candida spp. in patients receiving prophylaxis.

The availability of echinocandins has led to an expanded armamentarium of antifungal drugs with a potentially promising role as agents for targeted prophylaxis for invasive fungal infections in high-risk liver transplant recipients. Anidulafungin is unique amongst echinocandins in that it is eliminated from the body almost exclusively through biotransformation by slow non-enzymatic degradation in the blood, without hepatic metabolism or renal elimination. Anidulafungin has demonstrated good safety profile. We hypothesize that anidulafungin will be more effective and a better tolerated antifungal prophylactic agent in this setting.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Anidulafungin Versus Fluconazole for the Prevention of Invasive Fungal Infections in High-risk Liver Transplant Recipients: a Randomized, Double-blind Trial
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: anidulafungin anti-fungal agent	Drug: Anidulafungin; 200 mg IV loading dose followed by 100 mg qd for 21 days; Other Names: Eraxis
Active Comparator: Fluconazole anti-fungal agent	Drug: Fluconazole; 400 mg IV for 21 days; Other Names: DIFLUCAN

Outcome Measures

Primary Outcome Measures

1. Frequency of Fungal Infection [90 days post enrollment]

Secondary Outcome Measures

1. Need for Additional Antifungal Therapy [90 days post enrollment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Liver transplant recipient at increased risk for infection increased risk include any of the following:

• retransplantation

• renal replacement therapy (dialysis),

• post transplant abdominal surgery (within 21days)

• receipt of corticosteroids for greater than 14 days within the 4 weeks -preceding transplant

• ICU care for greater than 48 hours at the time of transplantation

• colonization with Candida sps within 4 weeks of transplantation

• requirement of 15 units or greater of packed red cell transfusions

• Intraoperative time exceeding 6 hours

Exclusion Criteria:

• Hypersensitivity to azole or echinocandin antifungal agents

• receipt of systemic antifungal therapy within 4 weeks prior to transplantation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Cente	Los Angeles	California	United States	90095
2	University of Miami	Miami	Florida	United States	33136
3	University of Michigan	Ann Arbor	Michigan	United States	48109
4	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
5	University of Washington Medical Center	Seattle	Washington	United States	98195
6	University of Wisconsin - Madison	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Pittsburgh

Investigators

• Principal Investigator: Nina Singh, MD, University of Pittaburgh, VA Pittsburgh Health Systems

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nina Singh, MD, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00841971
• Other Study ID Numbers: PRO08110001
• First Posted: Feb 12, 2009
• Last Update Posted: Dec 17, 2014
• Last Verified: Dec 1, 2014

• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycoses; Fungemia; Lung Diseases, Fungal; Central Nervous System Fungal Infections; Lung Diseases; Fluconazole; Anidulafungin

Study Results

Participant Flow

Arm/Group Title	Anidulafungin	Fluconazole
Arm/Group Description	anti-fungal agent Anidulafungin: 200 mg IV loading dose followed by 100 mg qd for 21 days	anti-fungal agent Fluconazole: 400 mg IV for 21 days
Period Title: Overall Study
STARTED	100	100
COMPLETED	98	99
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Anidulafungin	Fluconazole	Total
Arm/Group Description	anti-fungal agent Anidulafungin: 200 mg IV loading dose followed by 100 mg qd for 21 days	anti-fungal agent Fluconazole: 400 mg IV for 21 days	Total of all reporting groups
Overall Participants	100	100	200
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	89 89%	89 89%	178 89%
>=65 years	11 11%	11 11%	22 11%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	58	58	58
Sex: Female, Male (Count of Participants)
Female	33 33%	28 28%	61 30.5%
Male	67 67%	72 72%	139 69.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	27 27%	38 38%	65 32.5%
Not Hispanic or Latino	73 73%	62 62%	135 67.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	100 100%	100 100%	200 100%

Outcome Measures

1. Primary Outcome

Title	Frequency of Fungal Infection
Time Frame	90 days post enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anidulafungin	Fluconazole
Arm/Group Description	anti-fungal agent Anidulafungin: 200 mg IV loading dose followed by 100 mg qd for 21 days	anti-fungal agent Fluconazole: 400 mg IV for 21 days
Measure Participants	98	99
Number [participants]	5 5%	8 8%

2. Secondary Outcome

Title	Need for Additional Antifungal Therapy
Time Frame	90 days post enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anidulafungin	Fluconazole
Arm/Group Description	anti-fungal agent Anidulafungin: 200 mg IV loading dose followed by 100 mg qd for 21 days	anti-fungal agent Fluconazole: 400 mg IV for 21 days
Measure Participants	98	99
Number [participants]	11 11%	11 11%

Adverse Events

Arm/Group Title	Anidulafungin		Fluconazole
Arm/Group Description	anti-fungal agent Anidulafungin: 200 mg IV loading dose followed by 100 mg qd for 21 days		anti-fungal agent Fluconazole: 400 mg IV for 21 days
All Cause Mortality
	Anidulafungin		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Anidulafungin		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/98 (1%)		0/99 (0%)
Cardiac disorders
Prolonged QT interval	1/98 (1%)	1	0/99 (0%)	0
Other (Not Including Serious) Adverse Events
	Anidulafungin		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/98 (11.2%)		11/99 (11.1%)
General disorders
deaths	11/98 (11.2%)	11	11/99 (11.1%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.