Steroids In Eosinophil Negative Asthma
- Conditions
- Asthma
- Interventions
- Registration Number
- NCT02066298
- Lead Sponsor
- Milton S. Hershey Medical Center
- Brief Summary
Because approximately half of all mild-moderately-severe asthma is persistently non-eosinophilic, it is important to determine prospectively if patients who are persistently non-eosinophilic differ in their benefit from inhaled corticosteroid treatment compared to patients who are not persistently non-eosinophilic.
- Detailed Description
SIENA is a 42-week randomized, stratified, 3-period double-blind placebo-controlled crossover study of patients with symptomatic mild-to-moderate asthma, not already taking an inhaled corticosteroid, in whom the effect of "medium-dose" inhaled corticosteroid (ICS) will be compared with the effect of placebo and with a long-acting muscarinic antagonist (LMA).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 295
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Physician-diagnosed asthma for at least previous 12 months.
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Able to perform reproducible spirometry.
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Baseline FEV1≥70% of predicted.
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Asthma confirmed either by:
- Beta-agonist reversibility to 4 puffs albuterol ≥ 12% OR
- Methacholine PC20 ≤ 16 mg/ml
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At least 1 of the following indications for chronic controller therapy:
- Asthma Symptoms > 2 days/week OR
- Nocturnal Asthma Symptoms > 2 nights/month OR
- Short-acting beta-agonist use for symptom control > 2 days/week
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For participants ≥18 years of age: Ability to provide informed consent. For participants under 18 years of age: Ability to provide verbal or written assent and ability of parent to provide informed consent.
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Willingness, if female and able to conceive, to utilize one medically-acceptable form of contraception.
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Chronic inhaled or oral corticosteroid therapy.
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Use of inhaled or oral corticosteroid therapy within 6 weeks.
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New allergen immunotherapy within the past 3 months or anticipated changes to an ongoing immunotherapy regimen.
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Use of omalizumab within 3 months.
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History of:
- bladder-neck obstruction, urinary retention or benign prostatic hyperplasia
- narrow angle glaucoma
- significant cardiovascular disorders and arrhythmias
- life-threatening asthma requiring treatment with intubation or mechanical ventilation within the past 5 years
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Respiratory tract infection within past 6 weeks.
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History of smoking within the past 1 year, or > 10 pack-years total if ≥ 18 years of age, or > 5 pack-years total if < 18 years of age.
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Chronic diseases or medical conditions (other than asthma) that could put the participant at risk by participation, e.g. chronic diseases of the lung (other than asthma), heart, liver, kidney, endocrine or nervous system, or immunodeficiency.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Mometasone then Placebo then Tiotropium Tiotropium Respimat 5mcg QD Mometasone 220mcg BID, followed by Placebo, followed by Tiotropium Respimat 5mcg QD Placebo then Mometasone then Tiotropium Mometasone 220mcg BID Placebo, followed by Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD Placebo then Tiotropium then Mometasone Mometasone 220mcg BID Placebo, followed by Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID Mometasone then Tiotropium then Placebo Tiotropium Respimat 5mcg QD Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD, followed by Placebo Mometasone then Tiotropium then Placebo Placebo Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD, followed by Placebo Placebo then Tiotropium then Mometasone Placebo Placebo, followed by Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID Tiotropium then Placebo then Mometasone Mometasone 220mcg BID Tiotropium Respimat 5mcg QD, followed by Placebo, followed by Mometasone 220mcg BID Mometasone then Tiotropium then Placebo Mometasone 220mcg BID Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD, followed by Placebo Mometasone then Placebo then Tiotropium Mometasone 220mcg BID Mometasone 220mcg BID, followed by Placebo, followed by Tiotropium Respimat 5mcg QD Placebo then Tiotropium then Mometasone Tiotropium Respimat 5mcg QD Placebo, followed by Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID Tiotropium then Placebo then Mometasone Tiotropium Respimat 5mcg QD Tiotropium Respimat 5mcg QD, followed by Placebo, followed by Mometasone 220mcg BID Tiotropium then Mometasone then Placebo Mometasone 220mcg BID Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID, followed by Placebo Tiotropium then Mometasone then Placebo Placebo Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID, followed by Placebo Mometasone then Placebo then Tiotropium Placebo Mometasone 220mcg BID, followed by Placebo, followed by Tiotropium Respimat 5mcg QD Placebo then Mometasone then Tiotropium Tiotropium Respimat 5mcg QD Placebo, followed by Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD Placebo then Mometasone then Tiotropium Placebo Placebo, followed by Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD Tiotropium then Placebo then Mometasone Placebo Tiotropium Respimat 5mcg QD, followed by Placebo, followed by Mometasone 220mcg BID Tiotropium then Mometasone then Placebo Tiotropium Respimat 5mcg QD Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID, followed by Placebo
- Primary Outcome Measures
Name Time Method Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1. End of 12-week treatment period This composite outcome uses a hierarchical method to ascertain differences in asthma control. For each participant, treatments are first compared to see if they differ in terms of treatment failures. If one treatment results in no treatment failures and another treatment does, it is deemed the superior treatment and no further comparisons are made. If treatment superiority cannot be assigned by treatment failures, then they are compared by asthma control days (ACDs). If one treatment yields at least 31 annualized ACDs more than another, it is deemed the superior treatment. If treatment superiority still cannot be assigned by ACDs, then they are compared by percent predicted FEV1 at the end of a treatment period. If one treatment yields at least 5% greater FEV1 than another, it is deemed the superior treatment. If treatment superiority cannot be assigned by exacerbations, ACDs or FEV1, then that participant is classified as having no differential response.
- Secondary Outcome Measures
Name Time Method Peak Expiratory Flow Rate End of 12-week treatment period Peak expiratory flow rate is a person's maximum speed of expiration. It measures the airflow through the bronchi and thus the degree of obstruction in the airways.
Treatment Failure End of 12-week treatment period Treatment Failure includes:
* Awakening from asthma three or more times in a two-week period or on two consecutive nights, or
* Using albuterol for relief of symptoms four or more times/day for two or more consecutive days, or
* Albuterol has been relieving symptoms for less than four hours after each treatment over a 12-hour period, or
* Using albuterol for relief of symptoms daily for seven days, and this use exceeds two times the weekly use of albuterol in the baseline period, or
* exercise induces unusual breathlessnessAnnualized Asthma Control Days End of 12-week treatment period Asthma Control Days (ACD) are based on patient completed electronic daily diaries, and are defined as: A day with no rescue albuterol use (pre-exercise albuterol will not be counted), no non-study asthma medications, no daytime asthma symptoms (shortness of breath, wheezing, chest tightness, phlegm/mucus rated as mild, moderate or severe, or cough rated as moderate or severe), no nighttime asthma symptoms, no unscheduled healthcare visits for asthma, and no PEF \< 80% of predetermined baseline. Annualized ACD are calculated as the proportion of ACD during the treatment period multiplied by 365.
Forced Expiratory Volume at One Second (FEV1) Percent of Predicted End of 12-week treatment period FEV1, expressed as percent of predicted FEV1 based on age, sex, race, and height.
Asthma Exacerbations End of 12-week treatment period Asthma exacerbations are more severe episodes of acute worsening, defined by meeting one or more of the following:
* FEV1 \<50% of baseline on 2 consecutive measurements
* FEV1 \<40% of predicted on 2 consecutive measurements
* Use of ≥ 16 puffs of "as needed" β-agonist per 24 hours for a period of 48 hours
* Use of oral/parenteral corticosteroid due to asthma
Trial Locations
- Locations (24)
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of Arizona College of Medicine
🇺🇸Tucson, Arizona, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
University of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
St. Louis Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Rainbow Babies and Children's Hospital, Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Ann and Robert H. Lurie Children's Hospital
🇺🇸Chicago, Illinois, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
North Carolina Clinical Research
🇺🇸Raleigh, North Carolina, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
UCSF Benioff Children's Hospital
🇺🇸San Francisco, California, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Nemours Children's Clinic
🇺🇸Orlando, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Duke University School of Medicine
🇺🇸Durham, North Carolina, United States