Tiotropium for Childhood Asthma

(TioNAAP Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Gerardo A Vazquez Garcia, MD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Nemours Children's Clinic

Must not be taking: Oral corticosteroids, ICS with LABA

Disqualifiers: Life-threatening asthma, Respiratory infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Most children with asthma have concurrent atopy (allergic inflammation), which is associated with an improved response to ICS. However, the absence of an atopic phenotype is associated with a poorer ICS response, leaving clinicians with limited treatment options. The nonatopic asthma phenotype has been characterized as the absence of atopic diseases including allergic rhinitis, eczema, or food allergies, and a negative skin prick test to common aeroallergens. Children with mild asthma treated with ICS over 44 weeks without a positive allergen skin test are 3 times more likely to have an asthma exacerbation when compared with children with positive skin tests. Similarly, adolescents and adults with asthma with low blood eosinophils or low sputum eosinophils have no difference in exacerbation rate response to ICS compared with placebo. Due to poor ICS response in nonatopic children and the known adverse effects of ICS, the development of non-steroid treatments options is needed. Monotherapy with the long-acting muscarinic antagonist, tiotropium, was superior to placebo for treatment failure outcomes in adolescents and adults with low sputum eosinophil levels. Tiotropium is approved in children as an add on therapy to ICS in children ≥ 6 years with asthma. But, this combination of treatment would still expose children with nonatopic asthma to the risks (but potentially without the benefit) of ICS therapy. The objective of this study is to conduct a feasibility pilot safety study of 6-weeks treatment with tiotropium monotherapy vs. ICS in children ages 6 to 11 years old with nonatopic mild persistent asthma.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot have used oral corticosteroids in the past 6 weeks or be using ICS with long-acting beta agonists or montelukast. You can continue using as-needed albuterol or low-dose ICS or daily montelukast.

What data supports the effectiveness of the drug Tiotropium Bromide for childhood asthma?

Research shows that Tiotropium Bromide, when added to regular asthma treatments, can improve lung function in children and adolescents with moderate to severe asthma. It is considered safe and effective for those who continue to have symptoms despite using inhaled corticosteroids. ^{1 2 3 4 5}

Is tiotropium safe for children with asthma?

Research shows that tiotropium is generally safe for children with asthma, with low and comparable rates of side effects to placebo. It has been studied in children aged 1-17 years, and the safety data supports its use as an add-on therapy for asthma. ^{2 3 4 6 7}

How is the drug Tiotropium Bromide different from other asthma treatments for children?

Tiotropium Bromide is unique because it is the only long-acting muscarinic antagonist (LAMA) approved for children aged 6 and older with severe asthma, offering a once-daily inhaled option that can improve lung function when other treatments like inhaled corticosteroids are not enough. ^{1 2 3 4 8}

Eligibility Criteria

This trial is for children aged 6 to 11 with mild, controlled nonatopic asthma—meaning they don't have allergies like hay fever, eczema or food allergies and their blood tests show low levels of certain immune cells and antibodies. They should be currently treated with as-needed albuterol, low-dose inhaled steroids or daily montelukast.

Inclusion Criteria

My asthma is under control.

You do not have allergies or asthma triggered by specific allergens, and you do not have a history of eczema or food allergies. Your blood test results for allergy-related markers are also within specific ranges.

I manage my mild asthma with daily medication or as-needed inhaler.

Exclusion Criteria

I use a combination inhaler or montelukast for my asthma.

Any other chronic diseases or medical conditions (other than asthma) that in the opinion of the investigator would prevent participation in a trial

I have had severe asthma needing a breathing tube or machine in the last 5 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Phase 1

Participants receive 6 weeks of treatment with either tiotropium or ICS

6 weeks

2 visits (in-person)

Washout

Participants undergo a 2-week washout period between treatments

2 weeks

1 visit (in-person)

Treatment Phase 2

Participants receive 6 weeks of treatment with the alternate therapy (tiotropium or ICS)

6 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Tiotropium Bromide (Anticholinergic)

Trial Overview The study compares tiotropium monotherapy—a long-acting inhaler medication—with inhaled corticosteroids (ICS) over a period of six weeks. It aims to see if tiotropium alone can manage asthma symptoms without the need for ICS in children who don't respond well to steroids due to lack of allergies.

Participant Groups

Group I: Tiotropium arm Experimental Treatment 1 Intervention

Subjects on this arm will start the study on tiotropium for 6 weeks. Received prescribed asthma controller medication for 2 weeks " washout" and complete 6 week on the prescribed asthma controller medication.

Group II: ICS arm Active Control 1 Intervention

Subjects on this arm will start the study on the prescribed asthma medication for 6 weeks. Received prescribed asthma controller medication for 2 weeks " washout" and complete 6 week on Tiotropium.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Nemours Specialty Care Jacksonville, FL

Who Is Running the Clinical Trial?

Nemours Children's Clinic Lead Sponsor

References

1. Pakistan pubmed.ncbi.nlm.nih.gov

Clinical efficacy of tiotropium in children with asthma. [2022] To investigate the clinical efficacy of tiotropium in children with asthma.

2. England pubmed.ncbi.nlm.nih.gov

Tiotropium bromide as adjunct therapy in children with asthma: a clinical experience. [2021] The Global Initiative for Asthma has only recently added tiotropium bromide as adjunct controller therapy in severe asthma (Step 4 or 5) in adults (2015) and children (2019). Although not yet approved for pediatric use by Health Canada, it has been occasionally offered by asthma specialists as a therapeutic trial in children with troublesome asthma or treatment for adverse effects. The objective of this study was to describe the indications and real-life clinical experience in initiating tiotropium in children with asthma.

3. Switzerland pubmed.ncbi.nlm.nih.gov

Tiotropium Bromide in Children and Adolescents with Asthma. [2018] Evidence is emerging on the use of long-acting muscarinic antagonists (LAMAs) in the management of asthma. Tiotropium bromide (Spiriva&#174; Respimat&#174;) is the only LAMA approved in children and adolescents. As the use of tiotropium becomes more common in clinical practice, it is necessary to review the existing data to identify patients who may benefit from the addition of this medication to their daily asthma regimen. This review discusses recent evidence on the safety and efficacy of tiotropium bromide in the management of asthma in children and adolescents. Current data support that tiotropium bromide has a bronchodilator effect, as evident by improvements in acute lung function compared with placebo; however, data are not yet available to present a stepwise approach or identify phenotypes that would benefit from the addition of tiotropium bromide. Well-designed studies are needed to compare the different step-up options to tiotropium bromide and provide an evidence-based stepwise approach for the management of asthma in children. Furthermore, study design should include identification of phenotypes that might experience a better clinical response to tiotropium bromide compared with other adjunct medications.

4. England pubmed.ncbi.nlm.nih.gov

Tiotropium in the management of paediatric and adolescent asthma: Systematic review. [2021] Tiotropium bromide is a long-acting muscarinic antagonist (LAMA) and is the only LAMA licensed for management for patients' ≥6 years old with severe asthma who have experienced one or more severe asthma exacerbations in the preceding year. Recent clinical trials have demonstrated that once-daily tiotropium is safe and efficacious in 6-17 year-olds with symptomatic asthma despite treatment with inhaled corticosteroids (ICSs), with or without additional controllers. In this paper, we review the evidence of the safety and efficacy of tiotropium add-on maintenance treatment in children and adolescents with symptomatic moderate and severe asthma.

5. United States pubmed.ncbi.nlm.nih.gov

Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. [2022] Results from phase III clinical trials in adults and phase II clinical trials in children and adolescents demonstrate that tiotropium is an effective treatment when added to inhaled corticosteroid (ICS) maintenance therapy.

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tiotropium in school-age children with moderate-to-severe symptomatic asthma: A systematic review. [2018] Label="BACKGROUND" NlmCategory="BACKGROUND">Recently published data support the benefits and safety of the once-daily (OD) long-acting anticholinergic tiotropium bromide bronchodilator for the treatment of uncontrolled moderate-to-severe asthma in adults and adolescents. However, its role for the treatment of school-age asthmatics has not yet been clearly defined. The aim of this systematic review was to assess the efficacy and safety of tiotropium Respimat&#174; in children aged 6-11&#160;years with moderate-to-severe symptomatic asthma.

7. England pubmed.ncbi.nlm.nih.gov

Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients. [2020] There remains an unmet need for effective, well-tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance.Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5&#8197;&#181;g versus placebo add-on therapy in patients with symptomatic asthma aged 1-17&#8197;years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30&#8197;days following treatment.Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5&#8197;&#181;g (51%), tiotropium 2.5&#8197;&#181;g (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or sex. The number of AEs related to asthma symptoms and exacerbations was lower with tiotropium (5&#8197;&#181;g) than with placebo, particularly during the seasonal peaks of these AEs.This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat add-on therapy in paediatric patients with symptomatic asthma.

8. Switzerland pubmed.ncbi.nlm.nih.gov

Update on Long-Acting Anticholinergics in Children and Adolescents With Difficult and Severe Asthma. [2022] Tiotropium bromide is the only long-acting muscarinic antagonist (LAMA) approved for treatment of patients aged ≥6 years old who have symptoms of uncontrolled asthma. Results from several clinical trials have found that once-daily inhaled tiotropium bromide is safe and efficacious in 6- to 17-year-olds with symptomatic asthma despite treatment with inhaled corticosteroids, with or without other medications. There are still few available studies investigating the impact of tiotropium bromide treatment in preschool children with suboptimal control. In this narrative review, we summarize the pharmacological effects of the LAMA tiotropium bromide, provide an overview about current asthma studies at different pediatric ages, and describe future research needs.