Clinical trial NCT02066298: Steroids In Eosinophil Negative Asthma
Official title: Steroids In Eosinophil Negative Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Mometasone
Tiotropium
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2014-02-19
Enrollment: 295
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1.
timeFrame: End of 12-week treatment period
Secondary outcomes:
measure: Treatment Failure
timeFrame: End of 12-week treatment period
measure: Annualized Asthma Control Days
timeFrame: End of 12-week treatment period
measure: Forced Expiratory Volume at One Second (FEV1) Percent of Predicted
timeFrame: End of 12-week treatment period
measure: Peak Expiratory Flow Rate
timeFrame: End of 12-week treatment period
measure: Asthma Exacerbations
timeFrame: End of 12-week treatment period
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital, Case Western Reserve University
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: William Busse, M.D.
role: STUDY_CHAIR
References:
citation: Lazarus SC, Krishnan JA, King TS, Lang JE, Blake KV, Covar R, Lugogo N, Wenzel S, Chinchilli VM, Mauger DT, Dyer AM, Boushey HA, Fahy JV, Woodruff PG, Bacharier LB, Cabana MD, Cardet JC, Castro M, Chmiel J, Denlinger L, DiMango E, Fitzpatrick AM, Gentile D, Hastie A, Holguin F, Israel E, Jackson D, Kraft M, LaForce C, Lemanske RF Jr, Martinez FD, Moore W, Morgan WJ, Moy JN, Myers R, Peters SP, Phipatanakul W, Pongracic JA, Que L, Ross K, Smith L, Szefler SJ, Wechsler ME, Sorkness CA; National Heart, Lung, and Blood Institute AsthmaNet. Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level. N Engl J Med. 2019 May 23;380(21):2009-2019. doi: 10.1056/NEJMoa1814917. Epub 2019 May 19.
citation: Sorkness CA, King TS, Dyer AM, Chinchilli VM, Mauger DT, Krishnan JA, Blake K, Castro M, Covar R, Israel E, Kraft M, Lang JE, Lugogo N, Peters SP, Wechsler ME, Wenzel SE, Lazarus SC; National Heart Lung and Blood Institute's "AsthmaNet". Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era. Contemp Clin Trials. 2019 Feb;77:98-103. doi: 10.1016/j.cct.2018.12.012. Epub 2018 Dec 27.