Ipratropium Bromide for Childhood Asthma

(T-RECS Trial)

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

44 Participants Needed

Trial Summary

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.

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

Research shows that combining Ipratropium Bromide with other asthma medications like beta 2 agonists (drugs that help open airways) can improve breathing and reduce the need for hospitalization in children with asthma attacks. It is especially helpful in providing more sustained relief compared to using beta 2 agonists alone. ^{1 2 3 4 5}

Is Ipratropium Bromide safe for use in children with asthma?

Ipratropium Bromide, also known as Atrovent, has been shown to be safe in studies with no significant side effects when used as an inhaler for asthma. However, some formulations with preservatives may cause adverse reactions, so preservative-free versions are recommended to reduce the risk of side effects. ^{6 7 8 9 10}

How is the drug Ipratropium Bromide unique in treating childhood asthma?

Ipratropium Bromide is unique because it is often combined with beta 2 agonists to provide more effective and sustained relief from asthma symptoms in children compared to using beta 2 agonists alone. Additionally, it can be administered conveniently through a metered-dose aerosol with a spacer and mask, which is as effective as nebulization but requires less time and equipment. ^{1 2 3 5 6}

What is the purpose of this trial?

Over 200,000 children have a 911 Emergency Medical Services (EMS) activation for respiratory distress each year, most of whom have acute wheezing. Early treatment in the prehospital setting could more rapidly relieve respiratory distress symptoms, prevent hypoxia, reduce invasive interventions, and reduce the need to be hospitalized, thereby facilitating earlier return to normal daily activities. Preliminary data from one site found hospital admission was reduced from 30% to 21% among children when an EMS system introduced a pediatric asthma protocol with oral dexamethasone. The current standard for Emergency Department (ED) treatment for acute wheezing for children two and older includes inhaled ipratropium and dexamethasone. These treatments have a longstanding history of safety and are effective in preventing hospitalization when used early in the ED. Specific treatment protocols generally direct prehospital care. Ipratropium and dexamethasone are recommended by national EMS organizations that develop model protocols for prehospital care. However, only 25% of EMS agencies from large US metropolitan areas allow ipratropium, and only 10% include dexamethasone in their treatment protocols. A clinical trial is critically needed to evaluate whether the significant EMS resources required to implement interventions for children with life-threatening wheezing that have proven benefit in the ED result in improved patient outcomes. The overall objective of this three-site pilot trial is to address specific questions related to the implementation of the study and ensure its feasibility. The study will be conducted in the Pediatric Emergency Care Applied Research Network (PECARN) EMS Affiliates (EMSAs). The investigators will include patients aged 2-17 who have a 911 call for acute life-threatening wheezing. The specific aims are 1) to develop and produce a prehospital checklist for the treatment bundle, including ipratropium and dexamethasone, 2) to determine the feasibility of collecting patient outcomes for wheezing children treated in the EMS system, and 3) to evaluate the implementation of the EMS treatment bundle and checklist using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Our overall hypothesis is that the study will be feasible to implement. This study will provide the necessary data to ensure the eventual trial is feasible, primarily by establishing the ability to measure the outcomes of interest as well as evaluating implementation. This study is innovative by focusing on pediatric care in the prehospital environment, a critical component of our emergency care system that is often neglected in research.

Research Team

Matthew Hansen, MD, MCR

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Value of ipratropium bromide in asthma crisis in children]. [2013]

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

Inhaled salbutamol plus ipratropium in moderate and severe asthma crises in children. [2013]

3. Pakistan pubmed.ncbi.nlm.nih.gov

Response to nebulized salbutamol versus combination with ipratropium bromide in children with acute severe asthma. [2017]

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

The effects of ipratropium bromide and fenoterol nebulizer solutions in children with asthma. [2017]

5. South Africa pubmed.ncbi.nlm.nih.gov

Ipratropium bromide delivered by metered-dose aerosol to infant wheezers. [2014]

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

Comparison of the efficacy of preservative free ipratropium bromide and Atrovent nebuliser solution. [2019]

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

The effect of vagolytic drugs on airway obstruction in patients with bronchial asthma. [2013]

8. Denmark pubmed.ncbi.nlm.nih.gov

Pharmacology and toxicology of Atrovent. [2013]

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

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

10. United States 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. [2013]