Efficacy Study of Fluconazole to Treat Coccidioidomycosis Pneumonia (Valley Fever)

NCT02663674 | Terminated Phase 4 Results FDA Drug

• 2 other identifiers: 14-0053HHSN272201300017I
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 9

Brief Summary

This is a Phase IV randomized, double-blinded, placebo-controlled study in 1000 individuals aged 18 years or older, with community acquired pneumonia (CAP) who meet all eligibility criteria in endemic regions. This study is designed to provide data on the effectiveness of early antifungal treatment (Fluconazole, 400 mg/day) for coccidioidomycosis pneumonia (also referred to as Valley Fever (VF) Pneumonia or acute onset valley fever) vs. placebo in subjects with coccidioidomycosis pneumonia. Patients who are prescribed antibacterials by their health care provider for acute CAP will be randomized to receive either placebo or 400 mg/day of fluconazole for 42 days. The primary objective is to assess the clinical response of early empiric antifungal therapy with fluconazole at Day 22 in subjects with coccidioidomycosis pneumonia and are compliant with the study intervention.

Conditions

Coccidioidomycosis

Keywords

CAP; Coccidioidomycosis; Community Acquired Pneumonia; FLEET; Fluconazole; Parent Study of 16-0008; Pneumonia; Valley Fever

Outcome Measures

Primary Outcomes (1)

• The Proportion of Participants Who Achieve a Clinical Response, Defined as at Least a 50% Reduction in Composite FLEET CAP Score From Baseline, in the Cocci-positive Per-protocol Population

  The Modified Scoring System for Evaluating Treatment Response in Early Coccidioidal Pneumonia (FLEET CAP) score is a clinical scoring system that allows a constellation of clinical symptoms to be quantified and scored over time: cough, fatigue, chest pain, dyspnea, sputum production, night sweats, fever and hypoxia. The recall period for symptom assessments was during the past week, with the exception of fever and hypoxia, which was measured on the day the FLEET CAP was administered. All symptoms are graded on a 0-3 severity scale, except for night sweats and hypoxia which are graded on a 0-2 severity scale, where 0 indicates the symptom is absent or normal. The range of total scores is from 0-22, where higher scores correspond to a worse outcome.

  Visit 2 (Day 20-23)

Secondary Outcomes (128)

• The Proportion of Participants Who Achieve a Clinical Response, Defined as at Least a 50% Reduction in Composite FLEET CAP Score From Baseline, in the Cocci Positive Modified Intent-to-Treat Population

  Visit 2 (Day 20-23)

• The Proportion of Participants Who Achieve a Clinical Response, Defined as at Least a 50% Reduction in Composite FLEET CAP Score From Baseline, in the All Randomized mITT Population

  Visit 2 (Day 20-23)

• The Proportion of Participants Who Achieve a Clinical Response, Defined as at Least a 50% Reduction in Composite FLEET CAP Score From Baseline, in All Randomized Participants Who Took at Least One Dose of Study Medication

  Visit 2 (Day 20-23)

• The Proportion of Participants Who Achieve a Clinical Response, Defined as at Least a 50% Reduction in Composite FLEET CAP Score From Baseline, in the Cocci Positive Modified Intent-to-Treat Population

  Visit 2 - Visit 4 (Day 20-46)

• The Proportion of Participants Who Achieve a Clinical Response, Defined as at Least a 50% Reduction in Composite FLEET CAP Score From Baseline, in All Randomized Participants Who Took at Least One Dose of Study Medication

  Visit 2 - Visit 4 (Day 20-46)

Study Arms (2)

Group 1

PLACEBO COMPARATOR

A single dose of Fluconazole placebo (2 capsules) administered orally once daily for 42 days starting on Day 1. N=500

Other: Placebo

Group 2

EXPERIMENTAL

400 mg of Fluconazole (2 capsules of 200 mg) administered orally once daily for 42 days starting on Day 1. N=500

Drug: Fluconazole

Interventions

Fluconazole DRUG

Fluconazole is a synthetic triazole antifungal agent. It will be supplied as 200 mg over encapsulated tablets. Each gelatin capsule will contain two-100 mg fluconazole tablets and microcrystalline cellulose for overfill.

Group 2

Placebo OTHER

Placebo will be supplied as matching gelatin capsules containing microcrystalline cellulose only. Capsules are the same size, weight, and color as capsules containing fluconazole tablets.

Group 1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged \> / = 18 years and presenting for clinical care in coccidioidomycosis endemic areas.
• Have a health care provider who has decided to treat community acquired pneumonia with antibacterials.
• Be able to take and tolerate oral antibacterials/antifungals.
• Able to understand the study and provide informed consent.
• Willing and able to comply with study procedures and complete study visits.
• Willing to allow access to medical records, and medical records are available to the study team.
• The first dosage of study drug will be administered within 72 hours of presentation for care.
• Able to swallow large pills.
• Sexually active female subjects must be of non-childbearing potential\* or, if of childbearing potential, must use a highly effective method of birth control\*\*(captured on the appropriate data collection form).
• \*Non-childbearing potential is defined as being post-menopausal for at least 18 months or surgically sterile via bilateral oophorectomy or hysterectomy.
• \*\*Female subjects must avoid becoming pregnant by using one of the following acceptable methods of birth control for 30 days prior to study drug dosing and must be maintained for 30 days after last dose of study drug: i. Intrauterine contraceptive device; OR ii. Oral contraceptives; OR iii. Implanon, Nexplanon, DepoProvera, contraceptive skin patch or NuvaRing; OR iv. Tubal ligation; OR v. Exclusively same-sex relationships.
• Non-pregnant female subjects of childbearing potential must have a negative pregnancy test within 24 hours prior to enrollment and at Visits 02 - 03.
• Subjects receiving any of the drugs reported to have manageable drug interactions with fluconazole are allowed to be enrolled based on PI clinical judgment.

You may not qualify if:

• Have recently received an experimental agent\* or participating in or planning to participate in a study involving an experimental agent\*\* while in the active drug administration phase of this study.
• \*defined as within 30 days prior to enrollment in this study.
• \*\*(e.g., vaccine, drug, biologic device, blood product, or medication).
• Present clinical diagnosis of hospital acquired pneumonia (HAP).
• Documented microbiologically- or serologically-confirmed past infection with coccidioidomycosis.
• Clinical diagnosis of coccidioidal infection that is of sufficient certainty as to exclude the need for antibacterial therapy.
• Have a history of systemic antibacterial treatment for this current CAP care episode occurring greater than 4 weeks prior to enrollment\*.
• \*Receipt of systemic antimicrobial therapy for indications other than respiratory tract infection is permitted.
• Have a history of systemic antifungal treatment within the 4 weeks prior to enrollment.
• A single dose of fluconazole (ex. treatment of vulvovaginal candidiasis) is acceptable and should not exclude subject from study.
• Long term use\* of high dose oral or parenteral glucocorticoids\*\*; or high-dose inhaled steroids\*\*\* taken within the 4 weeks prior to enrollment.
• \*defined as \> 8 weeks of daily use.
• \*\*high dose defined as prednisone \> / = 20 mg total daily dose, or equivalent dose of other glucocorticoids.
• \*\*\*high dose defined as \> 800 mcg/day of beclomethasone dipropionate or equivalent
• Have confirmed or suspected immunosuppression as a result of an underlying illness \[other than well controlled HIV infection\], primary immunodeficiency, or treatment, or induction/maintenance use of immunosuppressive agents\*.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (9)

Banner - University Medical Center Advanced Lung Disease Clinic - Phoenix

Phoenix, Arizona, 85006, United States

Location

St Josephs Hospital and Medical Center - Center for Liver Disease and Transplantation - Phoenix

Phoenix, Arizona, 85013, United States

Location

Mayo Clinic, Phoenix - Infectious Diseases

Phoenix, Arizona, 85054-4502, United States

Location

Mayo Clinic, Scottsdale - Infectious Diseases

Scottsdale, Arizona, 85259-5452, United States

Location

The University of Arizona - Banner University Medical Center Tucson Campus - Tucson

Tucson, Arizona, 85724-0001, United States

Location

Kaiser Permanente Chester Avenue Medical Offices - Pulmonology

Bakersfield, California, 93301, United States

Location

Kern Medical Center - Medicine

Bakersfield, California, 93306-4018, United States

Location

UCSF Fresno Center for Medical Education and Research - Clinical Research Center

Fresno, California, 93701, United States

Location

Kaiser Permanente Antelope Valley Medical Offices - Infectious Diseases

Lancaster, California, 93534, United States

Location

MeSH Terms

Conditions

Coccidioidomycosis; Community-Acquired Pneumonia; Pneumonia

Interventions

Fluconazole

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Community-Acquired Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The study terminated early due to low enrollment rates. When the study was stopped, 72 of a planned 1000 participants were enrolled and randomized; therefore, formal comparisons of the endpoints are not included.

Results Point of Contact

• Title: Emmanuel Walter, M.D., M.P.H.
• Organization: Duke Clinical Vaccine Unit

walte002@mc.duke.edu

919-620-5346

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 26, 2016
• Study Start: December 29, 2015
• Primary Completion: June 21, 2018
• Study Completion: July 31, 2018
• Last Updated: July 5, 2019
• Results First Posted: July 5, 2019

Record last verified: 2019-03

Locations

US (9)