Azithromycin for RSV-Induced Respiratory Failure

Recruiting at 10 trial locations

Overseen By Michele Kong, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Alabama at Birmingham

Must not be taking: Azithromycin, Macrolides

Disqualifiers: Cardiac disease, Immunosuppressive conditions, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 2 weeks

370 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 treat severe breathing problems caused by RSV, a virus responsible for respiratory infections in young children. Researchers believe Azithromycin might help by affecting a specific pathway in the body linked to the virus. Participants are divided into two groups: one receives Azithromycin, and the other receives a placebo, a harmless pill with no active ingredients, to compare results. Ideal participants are children under two years old in the pediatric ICU with RSV who need strong breathing support. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have used Azithromycin in the 7 days before ICU admission, you cannot participate.

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

Research has shown that Azithromycin (AZM) is generally safe for people. In one study, high doses of AZM were safe and helped reduce certain protein levels (MMP-9) in children on breathing machines. This suggests AZM might aid in serious breathing problems without causing harm. Another study found that various doses of AZM did not lead to negative side effects. Overall, these studies suggest that AZM is safe for most people, which is encouraging for those considering joining a trial. ^{1 2 3 4 5}

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

Unlike the standard treatments for RSV-induced respiratory failure, which primarily focus on supportive care like oxygen therapy and ventilation, Azithromycin offers a different approach. Researchers are excited about Azithromycin because it not only acts as an antibiotic but also possesses anti-inflammatory properties that may help reduce lung inflammation caused by RSV. This dual-action potential could lead to quicker recovery times and improved outcomes for patients suffering from severe respiratory issues due to RSV.

What evidence suggests that Azithromycin might be an effective treatment for RSV-induced respiratory failure?

Research suggests that Azithromycin (AZM) might help treat breathing problems caused by RSV. In this trial, participants in the AZM 20mg/kg Treatment Group will receive Azithromycin. One study found that high doses of AZM lowered MMP-9 levels in the airways of patients using breathing machines. Lower MMP-9 levels are believed to improve lung health. Another study showed that AZM was safe and might lead to better patient outcomes. While more research is needed, these findings suggest AZM could benefit those with RSV-related lung issues. ^{3 4 5 6 7}

Who Is on the Research Team?

Michele Kong, MD

Principal Investigator

The University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for children aged neonates to 2 years with RSV-induced respiratory failure, admitted to the ICU within 48 hours and requiring intensive breathing support. It's not for kids who've been on such support over 48 hours before ICU, have severe liver issues, chronic breathing needs at home, weakened immune systems, recent AZM use, heart problems or a history of pyloric stenosis.

Inclusion Criteria

I need a machine to help me breathe.

My symptoms started less than 5 days ago.

I am between 0-2 years old and was discharged home after birth if under 1 week old.

Exclusion Criteria

I have taken AZM within a week before being admitted to the ICU.

I have a heart condition or my heart beats irregularly with a QTc ≥ 450 ms.

I am not allergic to AZM or similar drugs and my liver functions are normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Azithromycin or placebo during acute hospitalization for RSV-induced respiratory failure

2 weeks

In-hospital treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including length of ICU stay and duration of oxygenation

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azithromycin

Trial Overview The ARRC trial tests if Azithromycin (AZM) helps children with acute RSV-induced respiratory failure in the ICU. Kids are randomly placed into two groups: one receiving AZM treatment and the other serving as a control group without AZM.

How Is the Trial Designed?

Group I: AZM 20mg/kg Treatment Group Active Control 1 Intervention

Group II: Control Group Placebo Group 1 Intervention

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?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Azithromycin is an effective antibiotic for treating respiratory infections in children, but it should be used cautiously due to concerns about antibiotic resistance, particularly with pneumococcal bacteria.

It is generally not recommended for certain conditions like acute pharyngitis, acute otitis media, or pneumococcal community-acquired pneumonia in children, especially in those at high risk for bacteremia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin use in paediatrics: A practical overview. Ovetchkine, P., Rieder, MJ.[2021]

Azithromycin (AZM) adjuvant therapy significantly reduces the time it takes for children with bronchiolitis to experience relief from wheezing and cough, based on a meta-analysis of 14 randomized controlled trials involving 1,318 children.

However, AZM does not significantly shorten the length of hospital stay or the duration of oxygen supply, indicating that while it may help with symptoms, it does not impact overall hospitalization time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical effect of azithromycin adjuvant therapy in children with bronchiolitis: a systematic review and Meta analysis]. Che, SY., He, H., Deng, Y., et al.[2020]

In a study of 55 patients with lower respiratory tract infections, azithromycin demonstrated a bacteriological cure rate of 70.8% and a clinical improvement rate of 69.09%, indicating its efficacy in treating these infections.

The medication was generally well tolerated, with minor side effects such as gastrointestinal disturbances (16.36%) and headaches (14.55%), and while 12.29% of patients experienced a reduction in platelet count, it was clinically insignificant and asymptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of safety and efficacy of azithromycin in lower respiratory tract infections (LRTI) Adhikari, P., Hegde, BM., Pereira, P., et al.[2020]

In a study of 3229 adult patients with respiratory infections, azithromycin was found to have a similar incidence of treatment-related adverse events (10.3%) compared to standard antibiotics (11.5%).

Azithromycin resulted in significantly fewer patient withdrawals due to adverse effects (0.4% vs. 2.1%), indicating it is well tolerated and a safe option for treating bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of azithromycin in the treatment of adults with community-acquired respiratory tract infections. Treadway, G., Pontani, D., Reisman, A.[2022]

In a study of 15 pediatric patients aged 1 to 10 years, azithromycin (AZM) demonstrated a high efficacy rate of 92.9% in treating various respiratory tract infections, including pneumonia and bronchitis.

The treatment was generally well-tolerated, with only one case of moderate diarrhea reported, indicating that AZM is a safe option for pediatric patients with respiratory infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical evaluations of azithromycin in the pediatric field]. Okada, T., Machida, Y., Fujieda, M., et al.[2016]

Prophylactic treatment with azithromycin significantly reduced weight loss and airway inflammation in RSV-infected mice, indicating its potential efficacy in managing RSV infections.

The treatment also lowered levels of inflammatory cytokines and reduced mortality in the RSV-infected group, suggesting that azithromycin could be a promising option for preventing severe outcomes in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model. Mosquera, RA., De Jesus-Rojas, W., Stark, JM., et al.[2019]

In a meta-analysis of randomized controlled trials involving 4,378 patients, azithromycin did not significantly reduce clinical failures in treating acute bronchitis and acute exacerbations of chronic bronchitis, indicating it may not be more effective than other antibiotics for these conditions.

However, azithromycin showed a significant reduction in clinical failures for community-acquired pneumonia, preventing approximately one clinical failure for every 50 patients treated, while maintaining a low discontinuation rate due to adverse events (0.7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections. Contopoulos-Ioannidis, DG., Ioannidis, JP., Chew, P., et al.[2019]

In a study of 60 patients with diffuse panbronchiolitis, azithromycin (AZM) showed an efficacy rate of 84.6%, with significant improvements in symptoms like sputum volume and dyspnea after 12 weeks of treatment.

The safety profile of AZM was favorable, with only 7.3% of patients experiencing mild to moderate adverse reactions, suggesting that long-term intermittent use of AZM could be as effective and safe as established treatments like erythromycin and clarithromycin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study on azithromycin in treatment of diffuse panbronchiolitis]. Kobayashi, H., Takeda, H., Sakayori, S., et al.[2019]

In a study of 3,995 patients aged 2-94, azithromycin demonstrated a favorable safety profile, with only 12.0% of patients experiencing side effects, which is significantly lower than the 14.2% seen with other standard antibiotics.

The most common side effects were mild to moderate gastrointestinal issues, and only 0.7% of patients discontinued treatment due to side effects, indicating that azithromycin is well tolerated even among patients with various concurrent illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical toleration and safety of azithromycin. Hopkins, S.[2022]

Azithromycin is an effective antimicrobial agent against common lower respiratory tract pathogens, showing superior activity against Haemophilus influenzae compared to other macrolides.

Clinical studies demonstrate that a short course of azithromycin (3 or 5 days) is as effective as a longer 10-day course of traditional antibiotics, which may improve patient compliance and reduce treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin in lower respiratory tract infections. Lode, H., Schaberg, T.[2013]

Single-dose azithromycin (30 mg/kg) demonstrated a high clinical success rate of 88% in treating children with otitis media, based on data from four clinical trials involving 619 patients.

The treatment was found to be safe, with mostly mild and temporary side effects, and showed excellent compliance rates of 99-100%, making it a suitable alternative for pediatric patients, especially in areas with low macrolide resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose azithromycin for the treatment of children with acute otitis media. Soley, CA., Arguedas, A.[2006]

Single-dose azithromycin (30 mg/kg) has been shown to be effective and safe for treating acute otitis media in children, with efficacy comparable to longer treatment regimens.

While promising results exist for single-dose azithromycin in adults for respiratory infections, more extensive studies are needed to confirm its effectiveness before it can be widely recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose azithromycin for respiratory tract infections. Law, C., Amsden, GW.[2007]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32324238/

A Phase 2 Randomized Clinical Trial - PubMed - NIH In this phase 2 randomized clinical trial, both doses of AZM were safe. While nasal MMP-9 levels were unchanged among treatment groups, endotracheal MMP-9 ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2764907

Azithromycin Treatment vs Placebo in Children With ... In this study, high doses of AZM were safe, reduced endotracheal MMP-9 levels in patients receiving mechanical ventilation, and potentially improved outcomes ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05026749

Azithromycin Treatment for Respiratory Syncytial Virus ... The proposed study will be a randomized, double-blinded, placebo-controlled Phase III trial to examine the efficacy of AZM therapy relative to placebo in ...

4. taggs.hhs.gov taggs.hhs.gov/Detail/AwardDetail?arg_AwardNum=R01HD105678&arg_ProgOfficeCode=50

Award Information | HHS TAGGS A Phase III Randomized Controlled Trial of Azithromycin for RSV-induced Respiratory Failure in Children - Lung disease caused by Respiratory Syncytial Virus ( ...

5. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2100069

Azithromycin to Prevent Recurrent Wheeze Following Severe ... Azithromycin therapy for 14 days during acute severe RSV bronchiolitis did not reduce recurrent wheeze occurrence over the following 2 to 4 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7180420/

Azithromycin Treatment vs Placebo in Children With ... In this study, high doses of AZM were safe, reduced endotracheal MMP-9 levels in patients receiving mechanical ventilation, and potentially ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02707523

Prospective Pilot Clinical Trial of Azithromycin Treatment In ... The study will include children with RSV infection who were admitted to the pediatric intensive care unit and require respiratory support via positive pressure ...