Azithromycin for Pediatric Health

(AVENIR Trial)

Overseen By Sandrine Kyane

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must not be taking: Macrolides

Disqualifiers: Allergy to macrolides, 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: 2 years

169707 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests giving an antibiotic called azithromycin to children aged 1-11 months in areas where many children die. The goal is to see if this reduces deaths by preventing infections. Azithromycin has been shown to reduce child mortality in various trials, particularly in sub-Saharan Africa.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the drug Azithromycin for pediatric health?

Azithromycin has been shown to be effective in treating respiratory infections in children, with a high success rate in conditions like pneumonia and bronchitis. In studies, it was found to be 'markedly effective' in 92.9% of cases and had a clinical success rate of 88% for treating ear infections in children. ^{1 2 3 4 5}

Is azithromycin safe for children?

Azithromycin is generally safe for children, with most side effects being mild or moderate, such as stomach issues. In studies, about 8.7% of children experienced side effects, which is similar to other antibiotics. Serious side effects are rare, and it can be safely used to treat bacterial infections in children. ^{1 6 7 8 9}

How is the drug azithromycin unique for treating pediatric conditions?

Azithromycin is unique because it can be given as a single-dose treatment for children with acute otitis media (ear infection), which helps with compliance, especially in areas with low resistance to the drug. It has a long half-life, meaning it stays in the body longer, allowing for less frequent dosing compared to other antibiotics. ^{1 3 10 11 12}

Research Team

Kieran O'Brien, PhD, MPH

Principal Investigator

University of California, San Francisco

Tom Lietman, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

The trial is for children aged 1-11 months in Niger, specifically from Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions. Caregivers must consent to participation. Children previously in MORDOR trials or with known macrolide allergies cannot join.

Inclusion Criteria

At the community-level: Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions

I am between 1-59 months or 7-12 years old, or I am the caregiver of an eligible child.

At the community-level: Verbal consent of community leader(s)

Exclusion Criteria

At the individual-level: Not on list of randomly selected participants from the census

At the community-level: Inaccessible or unsafe for study team

At the individual-level: Known allergy to macrolides

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers

2 years

Biannual visits for azithromycin distribution

Monitoring

Mortality and antimicrobial resistance monitored through birth histories and community/clinic visit data

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Azithromycin

Trial Overview Azithromycin for Oral Suspension is being tested to see if it can reduce child mortality when given twice a year to infants. The study will also monitor the impact on antibiotic resistance within programmatic settings.

Participant Groups

Group I: Programmatic azithro 1-11 Active Control 1 Intervention

Biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers

Group II: no intervention Active Control 1 Intervention

No additional 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 California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Bill and Melinda Gates Foundation

Collaborator

Trials

428

Recruited

23,060,000+

Ministry of Health, Niger

Collaborator

Trials

3

Recruited

1,356,000+

Findings from Research

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]

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]

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]

In a study involving 32 pediatric patients, azithromycin (AZM) demonstrated a high efficacy rate of 96.7% in treating various bacterial infections, with 18 patients rated as having 'excellent' outcomes.

While AZM was generally well-tolerated, with only mild side effects reported, it is important to note some patients experienced slight changes in laboratory test results, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical studies on azithromycin in pediatrics]. Okamoto, T., Sekiguchi, T.[2016]

In a randomized controlled trial involving 56 children with cystic fibrosis, both low (5mg/kg/day) and high (15mg/kg/day) doses of azithromycin did not show significant differences in improving lung function (FEV1) or reducing pulmonary exacerbations over 12 months.

While children tolerated both doses well without significant side effects, the study found that stopping azithromycin led to an increase in pulmonary exacerbations, indicating that the benefits of the treatment may diminish shortly after discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term daily high and low doses of azithromycin in children with cystic fibrosis: a randomized controlled trial. Kabra, SK., Pawaiya, R., Lodha, R., et al.[2010]

A meta-analysis of nine studies involving 3,597 pediatric patients found that azithromycin has a statistically significant lower risk of adverse events compared to other antibiotics, indicating its relative safety in treating infectious diseases in children.

While azithromycin is generally safe, caution is advised with higher dosages, suggesting that careful monitoring is necessary to avoid potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of azithromycin in pediatric infectious diseases: a clinical systematic review and meta-analysis. Li, D., Wang, Y.[2022]

A meta-analysis of 14 studies showed that azithromycin (AZM) has a significantly lower incidence of adverse reactions (24.20%) compared to control treatments (48.05%), indicating a better safety profile for pediatric respiratory disease treatment.

AZM demonstrated fewer adverse reactions across various administration methods, including sequential therapy, intravenous, and oral routes, making it a safer and more appealing option for treating children with respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profiles and adverse reactions of azithromycin in the treatment of pediatric respiratory diseases: A systematic review and meta-analysis. Sun, YW., Cen, YH., Chen, MH., et al.[2023]

In a review of 45 studies involving 4,499 children aged 6 months to 16 years, azithromycin was found to be safe for treating acute bacterial infections, with only 8.7% of children experiencing mild to moderate adverse events, primarily gastrointestinal.

The incidence of adverse events was similar between azithromycin and comparator treatments, with only 1.3% of azithromycin-treated children discontinuing treatment due to side effects, indicating its comparable safety profile to other antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paediatric safety of azithromycin: worldwide experience. Treadway, G., Pontani, D.[2019]

Azithromycin significantly reduces the risk of bronchopulmonary dysplasia (BPD) in extremely premature neonates, with a relative risk of 0.83 based on a review of 11 studies involving 473 neonates.

While azithromycin is associated with various adverse events, including respiratory and gastrointestinal issues, there was no significant increase in liver enzyme levels compared to placebo, indicating a relatively safe profile for this medication in neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and safety of azithromycin in neonates: a systematic review. Smith, C., Egunsola, O., Choonara, I., et al.[2022]

Azithromycin (AZM) was effective in treating various pediatric infections, achieving a success rate of 94.4% in 36 patients, including those with pneumonia and bronchitis.

The treatment was well-tolerated with no observed adverse reactions or abnormal laboratory changes in a safety evaluation of 43 patients, indicating its safety for use in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of a new macrolide antibiotic, azithromycin, in the pediatric field]. Meguro, H., Terashima, I.[2016]

This systematic review aims to comprehensively evaluate the safety of azithromycin in children of all ages by analyzing various study types, including randomized controlled trials and cohort studies, to identify any adverse drug reactions (ADRs).

Concerns about the safety of azithromycin, particularly in young children, will be addressed through meta-analyses and subgroup analyses based on age and dosage, ensuring a thorough assessment of its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of azithromycin in paediatrics: a systematic review protocol. Xu, P., Zeng, L., Xiong, T., et al.[2023]

In a study involving 35 children aged 9 months to 12 years, azithromycin (AZM) demonstrated a high efficacy rate of 93.9% in treating various pediatric infectious diseases, including pharyngotonsillitis and pneumonia.

The treatment was generally safe, with only a few cases of elevated liver enzymes reported and no significant clinical adverse reactions observed, indicating that AZM can be a reliable option for pediatric infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical evaluation of azithromycin in the pediatric field]. Kitamura, K., Kamiya, H., Nakano, T., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Azithromycin use in paediatrics: A practical overview. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical evaluations of azithromycin in the pediatric field]. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Single-dose azithromycin for the treatment of children with acute otitis media. [2006]

4. Japan pubmed.ncbi.nlm.nih.gov

[Clinical studies on azithromycin in pediatrics]. [2016]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term daily high and low doses of azithromycin in children with cystic fibrosis: a randomized controlled trial. [2010]

6. China pubmed.ncbi.nlm.nih.gov

Safety of azithromycin in pediatric infectious diseases: a clinical systematic review and meta-analysis. [2022]

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

Safety profiles and adverse reactions of azithromycin in the treatment of pediatric respiratory diseases: A systematic review and meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Paediatric safety of azithromycin: worldwide experience. [2019]

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

Use and safety of azithromycin in neonates: a systematic review. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of a new macrolide antibiotic, azithromycin, in the pediatric field]. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Safety of azithromycin in paediatrics: a systematic review protocol. [2023]

12. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical evaluation of azithromycin in the pediatric field]. [2016]