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Completed

NCT Number: NCT02066298

Steroids In Eosinophil Negative Asthma

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.

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Key information

Conditions

Asthma Bronchial Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Arizona College of Medicine, Tucson, Arizona, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Physician-diagnosed asthma for at least previous 12 months.
  • Able to perform reproducible spirometry.
  • Baseline FEV1≥70% of predicted.
  • Asthma confirmed either by:
  • Beta-agonist reversibility to 4 puffs albuterol ≥ 12% OR
  • Methacholine PC20 ≤ 16 mg/ml
  • 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
  • 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.
  • Willingness, if female and able to conceive, to utilize one medically-acceptable form of contraception.

Exclusion criteria

  • Chronic inhaled or oral corticosteroid therapy.
  • Use of inhaled or oral corticosteroid therapy within 6 weeks.
  • New allergen immunotherapy within the past 3 months or anticipated changes to an ongoing immunotherapy regimen.
  • Use of omalizumab within 3 months.
  • 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
  • Respiratory tract infection within past 6 weeks.
  • 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.
  • 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.

Treatment and study plan

Mometasone 220mcg BID

Drug

Mometasone is an ICS

Other names: Asmanex

Tiotropium Respimat 5mcg QD

Drug

Tiotropium is a LMA

Placebo

Drug

Primary outcomes

  1. Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1.

    Time frame: 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 outcomes

  1. Treatment Failure

    Time frame: 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 breathlessness

  2. Annualized Asthma Control Days

    Time frame: 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.

  3. Forced Expiratory Volume at One Second (FEV1) Percent of Predicted

    Time frame: End of 12-week treatment period

    FEV1, expressed as percent of predicted FEV1 based on age, sex, race, and height.

  4. Peak Expiratory Flow Rate

    Time frame: 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.

  5. Asthma Exacerbations

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Milton S. Hershey Medical Center

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Acronym: SIENA

Important dates

Study start
2014
Primary completion
2018
Study completion
2018
First posted
Feb 19, 2014
Registry last updated
May 29, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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