Azithromycin for Critical Asthma

(CR-AZI Kids Trial)

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

Trial Summary

What is the purpose of this trial?

The CR-AZI Study will assess the immunomodulatory effects of Azithromycin for pediatric Critical Asthma.

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.

What data supports the effectiveness of the drug Azithromycin for critical asthma?

Research shows that Azithromycin, an antibiotic, can reduce asthma flare-ups and improve quality of life for people with uncontrolled asthma, especially when added to standard treatments. However, its effectiveness can vary, and some studies did not find significant benefits in certain types of severe asthma. ^{1 2 3 4 5}

Is azithromycin safe for use in humans?

Azithromycin, also known as Zithromax or Zmax, has been studied for its safety in treating asthma. Research shows no significant difference in adverse events (unwanted side effects) when using azithromycin compared to not using it, suggesting it is generally safe for humans. ^{1 4 6 7 8}

How is the drug azithromycin unique in treating critical asthma?

Azithromycin is unique for critical asthma because it not only acts as an antibiotic but also has anti-inflammatory and immune-modulating effects, which can help reduce asthma exacerbations and improve quality of life, especially in patients with poorly controlled asthma. ^{1 2 5 7 9}

Research Team

Anthony Sochet, MD

Principal Investigator

Johns Hopkins All Children's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

[Long-term macrolide therapy in asthma]. [2021]

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

Amazing pleiotropic effects of azithromycin. [2020]

3. England 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. [2023]

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

The efficacy and safety of azithromycin in asthma: A systematic review. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Add-on azithromycin reduces sputum cytokines in non-eosinophilic asthma: an AMAZES substudy. [2021]

6. United States 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. [2022]

7. China pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of azithromycin in the treatment of bronchial asthma: a meta-analysis]. [2018]

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

The efficacy and safety of azithromycin in treatment for childhood asthma: A systematic review and meta-analysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. [2022]