Steroids In Eosinophil Negative Asthma

NCT02066298 | Completed Phase 3 Results DMC

• 2 other identifiers: AsthmaNet 0071U10HL098115
• Study Type: interventional
• Target: 295
• Locations: 1 country
• Sites: 25

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.

Conditions

Asthma

Keywords

Asthma; Mometasone; Tiotropium

Outcome Measures

Primary Outcomes (1)

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

  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 Outcomes (5)

• Treatment Failure

  End of 12-week treatment period

• Annualized Asthma Control Days

  End of 12-week treatment period

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

  End of 12-week treatment period

• Peak Expiratory Flow Rate

  End of 12-week treatment period

• Asthma Exacerbations

  End of 12-week treatment period

Study Arms (6)

Mometasone then Tiotropium then Placebo

EXPERIMENTAL

Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD, followed by Placebo

Drug: Mometasone 220mcg BID; Drug: Tiotropium Respimat 5mcg QD; Drug: Placebo

Mometasone then Placebo then Tiotropium

EXPERIMENTAL

Mometasone 220mcg BID, followed by Placebo, followed by Tiotropium Respimat 5mcg QD

Drug: Mometasone 220mcg BID; Drug: Tiotropium Respimat 5mcg QD; Drug: Placebo

Placebo then Mometasone then Tiotropium

EXPERIMENTAL

Placebo, followed by Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD

Drug: Mometasone 220mcg BID; Drug: Tiotropium Respimat 5mcg QD; Drug: Placebo

Placebo then Tiotropium then Mometasone

EXPERIMENTAL

Placebo, followed by Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID

Drug: Mometasone 220mcg BID; Drug: Tiotropium Respimat 5mcg QD; Drug: Placebo

Tiotropium then Placebo then Mometasone

EXPERIMENTAL

Tiotropium Respimat 5mcg QD, followed by Placebo, followed by Mometasone 220mcg BID

Drug: Mometasone 220mcg BID; Drug: Tiotropium Respimat 5mcg QD; Drug: Placebo

Tiotropium then Mometasone then Placebo

EXPERIMENTAL

Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID, followed by Placebo

Drug: Mometasone 220mcg BID; Drug: Tiotropium Respimat 5mcg QD; Drug: Placebo

Interventions

Mometasone 220mcg BID DRUG

Mometasone is an ICS

Also known as: Asmanex

Mometasone then Placebo then Tiotropium; Mometasone then Tiotropium then Placebo; Placebo then Mometasone then Tiotropium; Placebo then Tiotropium then Mometasone; Tiotropium then Mometasone then Placebo; Tiotropium then Placebo then Mometasone

Tiotropium Respimat 5mcg QD DRUG

Tiotropium is a LMA

Mometasone then Placebo then Tiotropium; Mometasone then Tiotropium then Placebo; Placebo then Mometasone then Tiotropium; Placebo then Tiotropium then Mometasone; Tiotropium then Mometasone then Placebo; Tiotropium then Placebo then Mometasone

Placebo DRUG

Mometasone then Placebo then Tiotropium; Mometasone then Tiotropium then Placebo; Placebo then Mometasone then Tiotropium; Placebo then Tiotropium then Mometasone; Tiotropium then Mometasone then Placebo; Tiotropium then Placebo then Mometasone

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (25)

University of Arizona College of Medicine

Tucson, Arizona, 85724, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94143, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Clinic

Orlando, Florida, 32827, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Ann and Robert H. Lurie Children's Hospital

Chicago, Illinois, 60614, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27110, United States

Location

North Carolina Clinical Research

Raleigh, North Carolina, 27607, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Rainbow Babies and Children's Hospital, Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

• Covar R, Lazarus SC, Krishnan JA, Blake KV, Sorkness CA, Dyer AM, Lang JE, Lugogo NL, Mauger DT, Wechsler ME, Wenzel SE, Cardet JC, Castro M, Israel E, Phipatanakul W, King TS; National Heart, Lung, and Blood Institute AsthmaNet. Association of Sputum Eosinophilia With Easily Measured Type-2 Inflammatory Biomarkers in Untreated Mild Persistent Asthma. J Allergy Clin Immunol Pract. 2024 Apr;12(4):960-969.e6. doi: 10.1016/j.jaip.2023.12.010. Epub 2023 Dec 12.

  PMID: 38097180 DERIVED

• 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.

  PMID: 31112384 DERIVED

• 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.

  PMID: 30593883 DERIVED

Related Links

• AsthmaNet

MeSH Terms

Conditions

Asthma

Interventions

Mometasone Furoate; BID protein, human

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: David Mauger
• Organization: Penn State University

dmauger@psu.edu

717-531-7178

Study Officials

• William Busse, M.D.

  University of Wisconsin, Madison

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, AsthmaNet Data Coordinating Center

Study Record Dates

• First Submitted: February 10, 2014
• First Posted: February 19, 2014
• Study Start: July 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: May 29, 2019
• Results First Posted: April 18, 2019

Record last verified: 2019-05

Locations

US (25)