Azithromycin for Critical Asthma

(CR-AZI Kids Trial)

Recruiting at 1 trial location

Overseen By Alexa R Roberts, MD

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Johns Hopkins All Children's Hospital

Must be taking: Beta-agonists, Corticosteroids

Must not be taking: Azithromycin, Macrolides

Disqualifiers: Congenital heart disease, Arrhythmias, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Azithromycin, a common antibiotic, can help children with severe asthma in the Pediatric Intensive Care Unit (PICU). The researchers aim to determine if it can control asthma by affecting the immune system. Participants will be divided into two groups: one will receive Azithromycin, and the other will receive standard asthma care without the antibiotic. Children aged 3 to 17 admitted to the PICU with critical asthma and on certain asthma medications are suitable for this trial. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval. It offers participants a chance to contribute to potentially groundbreaking advancements in asthma care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking Azithromycin or similar antibiotics.

Is there any evidence suggesting that Azithromycin is likely to be safe for humans?

Research shows that azithromycin is generally safe for use. Prospective trial participants should know that the FDA has approved azithromycin for treating bacterial infections, indicating its safety is well understood.

In studies with asthma patients, more than half who took azithromycin saw improvements. However, some trials did not show significant help with asthma control, though no major safety issues arose. This suggests that while it might not always aid asthma, it is not linked to serious side effects.

The trial is in a mid-to-late stage, indicating azithromycin's success in earlier studies. However, it is important to note that it hasn't consistently improved asthma symptoms. Participants can feel confident about the drug's safety but should be aware that its effectiveness for asthma can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Unlike the standard treatments for critical asthma, which often rely on inhaled corticosteroids and bronchodilators, Azithromycin offers a unique approach by being an antibiotic with potential anti-inflammatory effects. Researchers are excited about Azithromycin because it could reduce airway inflammation more quickly, potentially leading to faster relief of asthma symptoms. While typical treatments can take weeks to show effectiveness, Azithromycin might deliver results in just a few days, which is particularly promising for patients in critical condition.

What evidence suggests that Azithromycin might be an effective treatment for critical asthma?

Research has shown that azithromycin might help reduce severe asthma attacks. In one study, adults with asthma experienced 40% fewer attacks and respiratory infections when using this medication. Another study found that more than half of the adults taking azithromycin saw their asthma symptoms greatly improve or even disappear. However, not all studies agree, as some did not find significant benefits for asthma with azithromycin. In this trial, participants in the Azithromycin Intervention arm will receive azithromycin to evaluate its effectiveness further. Meanwhile, those in the Standard Care arm will receive standard care without azithromycin. Overall, promising evidence suggests that azithromycin may help manage asthma symptoms, but results can vary. ^{2 4 6 7 8}

Who Is on the Research Team?

Anthony Sochet, MD

Principal Investigator

Johns Hopkins All Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children aged 3-17 who are in the Pediatric Intensive Care Unit (PICU) with a primary diagnosis of critical asthma. They must be prescribed continuous inhaled or IV beta-agonist therapy and IV systemic corticosteroids to participate.

Inclusion Criteria

I am between 3 and 17 years old.

I have been admitted to the Pediatric Intensive Care Unit.

I am prescribed IV corticosteroids.

Exclusion Criteria

Tracheostomy Dependence at Admission

I am currently taking azithromycin or similar antibiotics.

My heart condition from birth has not been treated with surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive Azithromycin 10mg/kg/dose (max dose 500mg) once daily for 3 days

3 days

Daily visits during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Azithromycin

Trial Overview The CR-AZI Study is testing the effects of Azithromycin, an antibiotic that may also help control inflammation, on children with severe asthma to see if it can improve their condition.

How Is the Trial Designed?

Group I: Azithromycin Intervention Experimental Treatment 1 Intervention

Participants in this arm will receive Azithromycin 10mg/kg/dose (max dose 500mg) once daily for 3 days.

Group II: Standard Care Active Control 1 Intervention

Participants will receive standard care without Azithromycin.

Azithromycin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Approved in United States as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Approved in Canada as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Who Is Running the Clinical Trial?

Johns Hopkins All Children's Hospital

Lead Sponsor

Trials

47

Recruited

5,009,000+

Published Research Related to This Trial

Azithromycin, a type of macrolide antibiotic, has been shown to effectively reduce asthma exacerbations and improve quality of life in patients with both eosinophilic and non-eosinophilic asthma, based on randomized controlled trials.

The GINA report recommends azithromycin as an add-on therapy for patients with uncontrolled severe asthma, particularly those not responding to high-dose inhaled corticosteroids or biologic treatments, although its effectiveness may vary in severe eosinophilic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term macrolide therapy in asthma]. Paçacı Çetin, G., Arslan, B., Yılmaz, İ.[2021]

Add-on azithromycin (AZM) significantly reduces asthma exacerbations in poorly controlled patients, regardless of their asthma type, based on a study involving a predefined substudy of the AMAZES protocol over 48 weeks.

AZM treatment notably decreased inflammatory proteins in sputum and reduced the presence of Haemophilus influenzae, particularly in patients with non-eosinophilic asthma, highlighting its anti-inflammatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Add-on azithromycin reduces sputum cytokines in non-eosinophilic asthma: an AMAZES substudy. Shukla, SD., Taylor, SL., Gibson, PG., et al.[2021]

Azithromycin as an add-on therapy for asthma showed a small but statistically significant improvement in forced expiratory volume in one second (FEV1), indicating a potential benefit in lung function.

However, azithromycin did not significantly reduce asthma exacerbations or improve other key measures like peak expiratory flow (PEF) or quality of life, although it did show a notable reduction in fractional exhaled nitric oxide (FeNO) levels among Asian asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of long-term add-on treatment of azithromycin in asthma: A systematic review and meta-analysis. Wang, X., Luo, J., Wang, D., et al.[2022]

Azithromycin (AZI) combined with standard asthma treatments significantly reduced the frequency of asthma exacerbations in children aged 6-14 years, showing a prevalence of 13% in the AZI group compared to 63% in the control group.

AZI also improved lung function and asthma control test scores in children with chronic persistent asthma, although the most common side effects were gastrointestinal issues, indicating a need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of azithromycin in treatment for childhood asthma: A systematic review and meta-analysis. Pan, X., Liu, Y., Luo, J., et al.[2022]

This study aims to systematically evaluate the efficacy of azithromycin as an add-on treatment for adults with persistent uncontrolled asthma, comparing it to standard treatments like inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs).

The primary outcomes will focus on the frequency of asthma exacerbations and changes in lung function, with a comprehensive review of randomized controlled trials to provide a robust analysis of azithromycin's potential benefits and safety in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin as an add-on treatment for persistent uncontrolled asthma in adults: protocol of a systematic review and meta-analysis. Liu, W., Mu, W., Zhang, H., et al.[2023]

A systematic review of seven randomized controlled trials involving 1520 asthma patients found that azithromycin did not significantly improve lung function or asthma symptoms compared to placebo.

The study also indicated that azithromycin did not increase the risk of adverse events, suggesting it is safe, but overall, it showed no beneficial clinical outcomes for asthma control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of azithromycin in asthma: A systematic review. Tian, BP., Xuan, N., Wang, Y., et al.[2023]

Azithromycin significantly improves peak expiratory flow (PEF), asthma control test (ACT) scores, and FEV1% in asthma patients, particularly in Chinese patients, based on a meta-analysis of eight randomized controlled trials.

The treatment is well tolerated with no severe adverse events reported, suggesting that azithromycin could be a beneficial adjuvant therapy for asthma, although it does not significantly enhance patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of azithromycin in the treatment of bronchial asthma: a meta-analysis]. Liu, L., Wang, GZ., Han, D., et al.[2018]

The AMAZES trial, a large randomized double-blind study, found that azithromycin 500 mg taken three times a week for 48 weeks significantly reduced asthma exacerbations in adults with persistent uncontrolled asthma.

Participants also reported improvements in their asthma-related quality of life, highlighting the potential benefits of azithromycin as a treatment option for managing asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amazing pleiotropic effects of azithromycin. Lahousse, L.[2020]

In a study involving participants with severe asthma, long-term low-dose azithromycin significantly reduced the rate of asthma exacerbations, with a reduction from 2.01 to 1.2 exacerbations per person-year compared to placebo.

Azithromycin also improved asthma-related quality of life and was well tolerated, with gastrointestinal symptoms being the most common side effect, supporting its use as an effective treatment option for severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. Gibson, PG., Yang, IA., Upham, JW., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6926362/

Efficacy of azithromycin in severe asthma from the ... It led to a 40% reduction in severe asthma exacerbations, and a similar reduction in respiratory tract infections, when adults with symptomatic ...

2. journal.chestnet.org journal.chestnet.org/article/S0012-3692(24)00284-8/fulltext

Effect of Azithromycin on Asthma Remission in Adults With ... In this study, adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment ...

3. journals.lww.com journals.lww.com/ebp/fulltext/2019/07000/does_the_addition_of_azithromycin_improve_outcomes.1.aspx

Does the addition of azithromycin improve outcomes in the... Azithromycin treatment does not improve outcomes in adults with acute asthma exacerbations. There is conflicting evidence if azithromycin improves outcomes ...

4. severeasthma.org.au severeasthma.org.au/azithromycin/

Azithromycin for Severe Asthma In clinical trials, azithromycin treatment for <3 months failed to improve asthma outcomes (9, 10) and no evidence was identified to support ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0012369224002848

Effect of Azithromycin on Asthma Remission in Adults With ... Over one-half of the study population treated with azithromycin achieved clinical remission and clinical remission plus lung function criteria. The remission ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6378181/

The efficacy and safety of azithromycin in asthma These findings demonstrate no beneficial clinical outcome of azithromycin in asthma control, and we propose that further prospective cohorts are warranted.

7. publications.aap.org publications.aap.org/hospitalpediatrics/article/14/6/e254/197302/Azithromycin-for-Pediatric-Critical-Asthma-A

Azithromycin for Pediatric Critical Asthma: A Multicenter ... The primary outcome was AZI prescribing assessed by calendar year and participating hospital center. Descriptive data included age, National ...

8. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2553295

Azithromycin for Acute Exacerbations of Asthma This randomized clinical trial examines whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit.