Tiotropium for Childhood Asthma

(TioNAAP Trial)

Overseen By Jennifer Gafford, RN

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Nemours Children's Clinic

Must not be taking: Oral corticosteroids, ICS with LABA

Disqualifiers: Life-threatening asthma, Respiratory infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

26 Participants Needed

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}

Research Team

Gerardo A Vazquez Garcia, MD

Principal Investigator

Nemours

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.

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

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.

Who Is Running the Clinical Trial?

Nemours Children's Clinic

Lead Sponsor

Trials

128

Recruited

18,000+

Findings from Research

In a study of 80 children with moderate persistent asthma, adding tiotropium to fluticasone propionate significantly improved lung function compared to fluticasone alone over 12 weeks.

Tiotropium also reduced the frequency of short-acting beta2-adrenoceptor agonist use and nighttime awakenings, with no severe adverse reactions reported, indicating it is a safe and effective option for managing asthma in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of tiotropium in children with asthma. Huang, J., Chen, Y., Long, Z., et al.[2022]

In a study of 34 children aged 1-17 with severe asthma, tiotropium bromide was primarily used as a substitute therapy rather than an additional treatment, showing significant benefits in controlling symptoms like coughing and difficulty breathing.

Most physicians and parents reported improvements in asthma control and lung function, particularly in children with chronic symptoms, although some expressed concerns about potential adherence issues due to the need for an additional inhaler.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium bromide as adjunct therapy in children with asthma: a clinical experience. Ridha, Z., Bédard, MA., Smyrnova, A., et al.[2021]

Tiotropium bromide (Spiriva® Respimat®) is the only long-acting muscarinic antagonist (LAMA) approved for use in children and adolescents with asthma, showing a bronchodilator effect that improves lung function compared to placebo.

Current evidence supports the efficacy of tiotropium in asthma management, but more well-designed studies are needed to establish a stepwise treatment approach and identify specific patient phenotypes that may benefit most from its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium Bromide in Children and Adolescents with Asthma. Raissy, HH., Kelly, HW.[2018]

Tiotropium bromide is a safe and effective add-on treatment for children and adolescents aged 6-17 with moderate to severe asthma, even when they are already using inhaled corticosteroids.

Clinical trials have shown that once-daily tiotropium significantly helps manage asthma symptoms and reduces the risk of severe exacerbations in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium in the management of paediatric and adolescent asthma: Systematic review. Sunther, M., Marchon, K., Gupta, A.[2021]

In a 48-week phase III trial involving 398 adolescents aged 12 to 17, once-daily tiotropium significantly improved lung function, as measured by peak FEV1, compared to placebo, with the 5-μg dose showing greater improvement (174 mL) than the 2.5-μg dose (134 mL).

Tiotropium was found to be safe and well tolerated when used as an add-on treatment to inhaled corticosteroids, indicating its potential as an effective therapy for managing moderate symptomatic asthma in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. Hamelmann, E., Bateman, ED., Vogelberg, C., et al.[2022]

Tiotropium Respimat® significantly improved lung function in children aged 6-11 with moderate-to-severe asthma, showing a peak FEV1 increase of 102 mL and a trough FEV1 increase of 82 mL compared to placebo, based on data from over 900 patients across three studies.

The treatment also led to a higher rate of asthma control (82.2% responders) and reduced the number of asthma exacerbations (29.1% vs. 39.8% with placebo), indicating its efficacy as an add-on therapy without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tiotropium in school-age children with moderate-to-severe symptomatic asthma: A systematic review. Rodrigo, GJ., Neffen, H.[2018]

In a pooled analysis of five studies involving 1691 pediatric patients aged 1-17 years, tiotropium (5 or 2.5 µg) was found to have a low incidence of adverse events (AEs), comparable to placebo, indicating it is a well-tolerated option for asthma management.

Tiotropium 5 µg significantly reduced asthma-related AEs and exacerbations compared to placebo, especially during peak seasons, suggesting it may provide effective symptom control in children with not fully controlled asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients. Vogelberg, C., Szefler, SJ., Vrijlandt, EJLE., et al.[2020]

Tiotropium bromide is a safe and effective long-acting muscarinic antagonist (LAMA) for treating uncontrolled asthma in children aged 6 to 17, even when they are already using inhaled corticosteroids.

There is a lack of research on the effects of tiotropium bromide in preschool children with asthma, highlighting a need for further studies in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Long-Acting Anticholinergics in Children and Adolescents With Difficult and Severe Asthma. Santamaria, F., Ziello, C., Lorello, P., et al.[2022]

References

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

Clinical efficacy of tiotropium in children with asthma. [2022]

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

Tiotropium bromide as adjunct therapy in children with asthma: a clinical experience. [2021]

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

Tiotropium Bromide in Children and Adolescents with Asthma. [2018]

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

Tiotropium in the management of paediatric and adolescent asthma: Systematic review. [2021]

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

Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. [2022]

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]

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

Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients. [2020]

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

Update on Long-Acting Anticholinergics in Children and Adolescents With Difficult and Severe Asthma. [2022]