Steroids In Eosinophil Negative Asthma (SIENA)

May 16, 2019 updated by: dave mauger, Milton S. Hershey Medical Center
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

295

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona College of Medicine
    • California
      • San Francisco, California, United States, 94143
        • University of California at San Francisco
      • San Francisco, California, United States, 94143
        • UCSF Benioff Children's Hospital
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic
      • Orlando, Florida, United States, 32827
        • Nemours Children's Clinic
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60614
        • Ann and Robert H. Lurie Children's Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University
      • Saint Louis, Missouri, United States, 63110
        • St. Louis Children's Hospital
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27110
        • Duke University School of Medicine
      • Raleigh, North Carolina, United States, 27607
        • North Carolina Clinical Research
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Children's Hospital, Case Western Reserve University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin-Madison

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Mometasone then Tiotropium then Placebo
Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD, followed by Placebo
Drug: Placebo
Drug: Mometasone 220mcg BID
Mometasone is an ICS
Other Names:
  • Asmanex
Drug: Tiotropium Respimat 5mcg QD
Tiotropium is a LMA
EXPERIMENTAL: Mometasone then Placebo then Tiotropium
Mometasone 220mcg BID, followed by Placebo, followed by Tiotropium Respimat 5mcg QD
Drug: Placebo
Drug: Mometasone 220mcg BID
Mometasone is an ICS
Other Names:
  • Asmanex
Drug: Tiotropium Respimat 5mcg QD
Tiotropium is a LMA
EXPERIMENTAL: Placebo then Mometasone then Tiotropium
Placebo, followed by Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD
Drug: Placebo
Drug: Mometasone 220mcg BID
Mometasone is an ICS
Other Names:
  • Asmanex
Drug: Tiotropium Respimat 5mcg QD
Tiotropium is a LMA
EXPERIMENTAL: Placebo then Tiotropium then Mometasone
Placebo, followed by Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID
Drug: Placebo
Drug: Mometasone 220mcg BID
Mometasone is an ICS
Other Names:
  • Asmanex
Drug: Tiotropium Respimat 5mcg QD
Tiotropium is a LMA
EXPERIMENTAL: Tiotropium then Placebo then Mometasone
Tiotropium Respimat 5mcg QD, followed by Placebo, followed by Mometasone 220mcg BID
Drug: Placebo
Drug: Mometasone 220mcg BID
Mometasone is an ICS
Other Names:
  • Asmanex
Drug: Tiotropium Respimat 5mcg QD
Tiotropium is a LMA
EXPERIMENTAL: Tiotropium then Mometasone then Placebo
Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID, followed by Placebo
Drug: Placebo
Drug: Mometasone 220mcg BID
Mometasone is an ICS
Other Names:
  • Asmanex
Drug: Tiotropium Respimat 5mcg QD
Tiotropium is a LMA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
End of 12-week treatment period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
End of 12-week treatment period
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.
End of 12-week treatment period
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.
End of 12-week treatment period
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.
End of 12-week treatment period
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
End of 12-week treatment period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Milton S. Hershey Medical Center

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Study Chair: William Busse, M.D., University of Wisconsin, Madison

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2014

Primary Completion (ACTUAL)

May 1, 2018

Study Completion (ACTUAL)

May 1, 2018

Study Registration Dates

First Submitted

February 10, 2014

First Submitted That Met QC Criteria

February 17, 2014

First Posted (ESTIMATE)

February 19, 2014

Study Record Updates

Last Update Posted (ACTUAL)

May 29, 2019

Last Update Submitted That Met QC Criteria

May 16, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AsthmaNet 007
  • 1U10HL098115 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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