Ipratropium Bromide for Childhood Asthma

(T-RECS Trial)

No longer recruiting at 2 trial locations

Overseen By Denise Griffiths

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Oregon Health and Science University

Must not be taking: Albuterol, Ipratropium, Dexamethasone

Disqualifiers: Pregnancy, Prisoner, Croup, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether administering the bronchodilator ipratropium bromide early to children with severe wheezing can improve their outcomes. The goal is to determine if using this treatment before hospital arrival can reduce the need for more intensive treatments and help children resume daily activities more quickly. The trial includes two groups: one receiving current standard care and the other receiving a new treatment bundle that includes ipratropium and a checklist for emergency responders. Children aged 2-17 who experience a 911 call for severe wheezing and asthma symptoms may be suitable candidates, particularly if they frequently have breathing difficulties or require the use of additional muscles to breathe. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ipratropium bromide is generally safe for children with asthma and can help reduce hospital visits. Studies indicate that adding ipratropium to other asthma treatments improves breathing and lowers the likelihood of hospitalization, particularly for children experiencing severe asthma attacks. For instance, one study found that 27.4% of children using ipratropium required hospitalization, compared to 36.5% of those who did not use it. This suggests that ipratropium is effective and well-tolerated in children.

Ipratropium is already part of standard emergency treatments in hospitals for children with sudden wheezing, demonstrating its safe use in many cases. Although the trial is still in an early phase, existing evidence supports its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new approach for treating childhood asthma. Unlike standard care, which typically involves inhaled corticosteroids or beta-agonists, this study tests a treatment bundle that includes Ipratropium Bromide, a bronchodilator that works by relaxing the muscles around the airways. This could potentially offer a faster and more targeted relief for asthma symptoms. The trial aims to determine if integrating this treatment into an EMS protocol improves patient outcomes, which could lead to more effective management strategies for childhood asthma.

What evidence suggests that this trial's treatments could be effective for childhood asthma?

Research has shown that ipratropium bromide, when combined with a beta2-agonist (a medicine that helps open the airways), can significantly improve lung function in children with asthma. Some studies suggest that using ipratropium alongside other asthma treatments may be more effective than using those treatments alone, particularly in severe cases. In one study, 93% of children using both ipratropium and another treatment improved, compared to 84% who used the other treatment alone, although this difference was not statistically significant. Ipratropium has been safely used for a long time in emergency situations to treat asthma. In this trial, one group will continue current care, while another will follow a new treatment protocol that includes ipratropium. Adding it to current treatments could potentially reduce hospitalization rates and help children with severe asthma attacks breathe better. ^{2 3 4 6 7}

Who Is on the Research Team?

Matthew Hansen, MD, MCR

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

This trial is for children aged 2-17 who experience severe asthma attacks and are transported by EMS after a 911 call. They must have a history of asthma or current symptoms, use accessory muscles to breathe, have an abnormal respiratory rate, or oxygen saturation below 93%. Children with allergies to the study drugs, pregnant individuals, prisoners, those with croup or foreign body in airway are excluded.

Inclusion Criteria

I experience agitation, drowsiness, or confusion.

I experience wheezing or have a silent chest when breathing.

I am between 2 and 17 years old.

Exclusion Criteria

Known or suspected pregnancy

History of albuterol, ipratropium, or dexamethasone allergy

Prisoner

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Prehospital Treatment

Implementation of a new treatment protocol with ipratropium and dexamethasone in the prehospital setting

Immediate intervention during EMS encounter

1 visit (in-person during EMS encounter)

Follow-up

Participants are monitored for safety and effectiveness after the prehospital treatment

1 week

Follow-up assessments within 6-8 days after EMS encounter

Outcome Evaluation

Evaluation of patient outcomes including hospital admission and critical care interventions

8 days

What Are the Treatments Tested in This Trial?

Interventions

• Ipratropium Bromide

Trial Overview The trial tests if early treatment with Ipratropium Bromide and dexamethasone given by EMS can help kids having serious asthma attacks. It aims to see if this approach reduces hospital admissions and improves outcomes compared to current protocols that don't widely include these treatments.

How Is the Trial Designed?

Group I: Treatment bundle and checklist Experimental Treatment 1 Intervention

In this arm, we will implement a new treatment protocol with the study bundle, and evaluate patient outcomes.

Group II: Continue current care Active Control 1 Intervention

In this arm, participants will be treated using the existing EMS protocol, and evaluate patient outcomes.

Ipratropium Bromide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Atrovent for:

• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm

Approved in United States as Atrovent for:

• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm

Approved in Canada as Combivent for:

• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm

Approved in Japan as Ipravent for:

• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

University at Buffalo

Collaborator

Trials

139

Recruited

105,000+

Wake Forest University Health Sciences

Collaborator

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

Ipratropium bromide effectively reduced respiratory rates and carbon dioxide levels in wheezing children under 25 months, with similar results for both nebulisation and metered-dose aerosol plus spacer methods.

The metered-dose aerosol method was found to be as effective as nebulisation but more convenient, requiring less time and equipment, and was well accepted by the children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipratropium bromide delivered by metered-dose aerosol to infant wheezers. Wesley, AG., Paruk, F., Broughton, MH., et al.[2014]

In a study involving 200 children with acute severe asthma, the combination of nebulised salbutamol and ipratropium bromide did not show a significant improvement in clinical outcomes compared to salbutamol alone.

While 93% of children receiving the combination treatment showed improvement, compared to 84% with salbutamol alone, the difference was not statistically significant, indicating that adding ipratropium may not provide additional benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to nebulized salbutamol versus combination with ipratropium bromide in children with acute severe asthma. Memon, BN., Parkash, A., Ahmed Khan, KM., et al.[2017]

Ipratropium bromide significantly protects against bronchoconstriction in asthmatic patients during various provocation tests, effectively doubling the number of breaths needed to trigger a significant drop in lung function (FEV1) for histamine and allergens, and increasing it sixfold for methacholine.

The treatment was well-tolerated with no reported side effects, indicating that ipratropium bromide is a safe option for preventing asthma-related bronchoconstriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The protective effect of ipratropium bromide aerosol against bronchospasm induced by hyperventilation and the inhalation of allergen, methacholine and histamine. Clarke, PS., Jarrett, RG., Hall, GJ.[2013]

Ipratropium bromide, when inhaled, effectively targets the airways with minimal side effects, making it a suitable treatment for conditions like asthma.

Toxicological studies indicate that while high doses can cause typical anticholinergic symptoms, inhalation at therapeutic levels does not impair lung function or structure, suggesting a safe profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and toxicology of Atrovent. Engelhardt, A.[2013]

Ipratropium bromide, when used alongside other bronchodilators, has shown to be more effective for asthma patients than using either treatment alone, indicating a beneficial combination therapy.

There have been no reported increases in side effects when ipratropium is combined with other bronchodilators, suggesting that this combination is safe for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant bronchodilator therapy and ipratropium bromide. A clinical review. Chervinsky, P.[2019]

Ipratropium bromide, when inhaled, has minimal absorption and side effects, making it a safe option for treating asthma in children.

Combining ipratropium bromide with beta 2 sympathomimetics leads to more effective and longer-lasting bronchodilation compared to using beta 2 sympathomimetics alone, suggesting it should be included in treatment plans for acute asthma in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Value of ipratropium bromide in asthma crisis in children]. Delacourt, C., de Blic, J., Lebourgeois, M., et al.[2013]

Atropine sulphate and ipratropium bromide are effective bronchodilators that do not cause significant side effects, making them safe options for patients.

Both drugs provide a bronchodilation effect comparable to salbutamol, particularly benefiting the large airways, which is crucial for treating respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of vagolytic drugs on airway obstruction in patients with bronchial asthma. Firstater, E., Mizrachi, E., Topilsky, M.[2013]

In a study of 97 children aged 2-18 with moderate to severe asthma crises, the combination of salbutamol and ipratropium bromide significantly improved lung function and clinical status compared to salbutamol alone.

Children receiving the combination treatment had a lower hospitalization rate (18.4%) compared to those treated with salbutamol only (43.8%), indicating that this combination therapy is particularly beneficial for managing severe asthma crises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled salbutamol plus ipratropium in moderate and severe asthma crises in children. Iramain, R., López-Herce, J., Coronel, J., et al.[2013]

A study involving 30 asthmatic subjects found that the commercially available isotonic ipratropium bromide (Atrovent) caused paradoxical bronchoconstriction in some patients due to preservatives like benzalkonium chloride and EDTA.

In contrast, a preservative-free ipratropium bromide solution led to significantly better bronchodilation, with a mean increase in FEV1 of 29.2%, compared to 18.5% for Atrovent, indicating that removing these preservatives enhances both safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of preservative free ipratropium bromide and Atrovent nebuliser solution. Rafferty, P., Beasley, R., Holgate, ST.[2019]

In children with asthma, the combination of nebulized ipratropium bromide and fenoterol showed a slightly greater improvement in peak expiratory flow compared to using either medication alone.

Over a month of treatment, there were no significant differences in overall symptoms or lung function between the combination therapy and fenoterol alone, suggesting that the combination may be beneficial for specific subgroups of asthmatics with large airway issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of ipratropium bromide and fenoterol nebulizer solutions in children with asthma. Freeman, J., Landau, LI.[2017]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK66330/

Efficacy of ipratropium bromide in acute childhood asthma Ipratropium bromide when used in conjunction with a beta2-agonist offers a significant improvement in percentage predicted FEV1 although there is no evidence ...

2. nejm.org nejm.org/doi/full/10.1056/NEJM199810083391503

Effect of Nebulized Ipratropium on the Hospitalization ... We found no similar reduction in hospitalization rates for children with moderate asthma. On the basis of our data, approximately seven children ...

3. withpower.com withpower.com/trial/phase-2-emergencies-2024-46156

Ipratropium Bromide for Childhood Asthma (T-RECS Trial) While 93% of children receiving the combination treatment showed improvement, compared to 84% with salbutamol alone, the difference was not statistically ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0237620

Combination of ipratropium bromide and salbutamol in ... IB + salbutamol may be more effective than salbutamol alone for the treatment of asthma in children and adolescents, especially in those with severe and ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34473916/

The use of ipratropium bromide for treating moderate to ... The use of ipratropium bromide for treating moderate to severe asthma exacerbations in pediatric patients in an emergency setting: A cost- ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11714074/

The use of ipratropium bromide for the management ... Ipratropium added to beta2-agonists improves lung function and also decreases hospitalization rates, especially among children with severe exacerbations of ...

7. ijponline.biomedcentral.com ijponline.biomedcentral.com/articles/10.1186/s13052-024-01675-0

Critical reappraisal of short-acting bronchodilators for pediatric ... The results demonstrated that combination therapy with ipratropium bromide and salbutamol significantly reduced the risk of hospitalization ...