Azithromycin for Meningococcal Disease

Overseen By Paulina Rebolledo, MD, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Systemic antibiotics

Disqualifiers: Pregnancy, Breastfeeding, Allergic reactions, 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: 3

Duration: 1 day

1120 Participants Needed

Trial Summary

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've taken antibiotics in the last 30 days.

What data supports the effectiveness of the drug Azithromycin for treating meningococcal disease?

Azithromycin has been studied for its ability to reduce the presence of Neisseria meningitidis (the bacteria causing meningococcal disease) in the nose and throat, which can help prevent the spread of the disease. Additionally, it has been used successfully in controlling outbreaks of meningococcal disease in schools. ^{1 2 3 4 5}

Is azithromycin safe for humans?

Azithromycin is generally safe for humans, with mild side effects like diarrhea and abdominal pain occurring in a small percentage of patients. Serious side effects are rare, and it is well tolerated across different ages and conditions. ^{1 6 7 8 9}

How is the drug azithromycin unique in treating meningococcal disease?

Azithromycin is unique because it can be used as a single-dose treatment, which may improve patient compliance compared to longer antibiotic courses. It also has excellent tissue penetration and a long half-life, allowing it to stay effective in the body for an extended period. ^{1 10 11 12 13}

What is the purpose of this trial?

The purpose of this study is to determine the effectiveness of azithromycin in the eradication of nasopharyngeal carriage of N. meningitidis

Research Team

Paulina Rebolledo, MD, MSc

Principal Investigator

Emory University

Eligibility Criteria

This trial is for individuals who carry the bacteria N. meningitidis in their nasopharynx but may not necessarily show symptoms of Meningococcal Disease. The specific eligibility criteria to participate are not provided.

Inclusion Criteria

Undergraduate and graduate students attending Emory University affiliated campuses who reside in university affiliated housing (for undergraduate/graduate) or in off-campus housing (undergraduates)

I can understand and agree to the study's procedures on my own.

Exclusion Criteria

University faculty and staff

Currently pregnant or breast feeding

History of immediate or moderate-to-severe allergic reactions to azithromycin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive a single oral dose of 500mg azithromycin

1 day

1 visit (in-person)

Follow-up

Participants are monitored for eradication of N. meningitidis carriage

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Azithromycin

Trial Overview The study aims to test if azithromycin, an antibiotic, can eliminate the carriage of N. meningitidis bacteria from the nasopharynx, potentially reducing the risk of developing Meningococcal Disease.

Participant Groups

Group I: Azithromycin Experimental Treatment 1 Intervention

Persons with microbiologic documentation of N. meningitidis carriage will receive a single, standard dose of 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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Georgia Department of Public Health

Collaborator

Trials

2

Recruited

1,400+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

Findings from Research

Azithromycin effectively controlled a meningococcal disease outbreak in preschool-aged children (99 children aged 3-5 years), demonstrating its efficacy as a chemoprophylactic agent.

Ciprofloxacin was found to be safe for children aged 6-16 years, with a low incidence of mild arthralgia (0.9% in children), indicating no serious or long-lasting side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Control of a school outbreak of serogroup B meningococcal disease by chemoprophylaxis with azithromycin and ciprofloxacin]. González de Aledo Linos, A., García Merino, J.[2013]

A study of 156 Neisseria meningitidis isolates in Bangladesh from 1999-2006 found that serogroup A was the most prevalent (97.7%), with a significant increase in invasive meningococcal disease cases occurring primarily among children and young adults between 2002-2004.

All isolates were susceptible to key antibiotics like penicillin and ceftriaxone, but there was a concerning rise in cotrimoxazole resistance from 50% to 100% and a temporary emergence of azithromycin resistance, highlighting the need for ongoing surveillance and updated treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing isolations of Neisseria meningitides serogroup A from blood and cerebrospinal fluid in Dhaka, Bangladesh, 1999-2006. Hossain, MA., Ahmed, D., Ahmed, T., et al.[2009]

In a study involving 500 nursing students in Cairo, azithromycin demonstrated a 93% eradication rate of Neisseria meningitidis from the nasopharynx, comparable to rifampin's rates of 95% and 91% at 1 and 2 weeks post-treatment, respectively.

Both azithromycin and rifampin were well-tolerated, with no significant side effects reported, suggesting that azithromycin could be a safe and effective alternative for preventing meningococcal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin compared with rifampin for eradication of nasopharyngeal colonization by Neisseria meningitidis. Girgis, N., Sultan, Y., Frenck, RW., et al.[2019]

In a study involving 30 communities in Tanzania, biannual treatment with single-dose azithromycin did not significantly reduce the prevalence of clinical malaria in preschool children compared to a placebo, suggesting limited efficacy against malaria.

While there was a decline in malaria positivity over time in both treatment groups, the placebo group showed a greater odds of decline in RDT-positivity, indicating that the effect of azithromycin on malaria may be temporary and not substantial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study. Bloch, EM., Munoz, B., Mrango, Z., et al.[2020]

In a study of 181 children under 15 years old with invasive meningococcal disease, the case fatality rate was found to be 11.6%, indicating a significant risk of mortality.

Among survivors, 33% reported at least one long-term health issue, such as learning difficulties, hearing impairment, and various neurological and behavioral deficits, highlighting the potential for serious lasting effects even after recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical features and long-term sequelae of invasive meningococcal disease in children. Stein-Zamir, C., Shoob, H., Sokolov, I., et al.[2022]

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]

Two cases of severe neuropsychiatric reactions, including hallucinations and seizures, were reported in two brothers aged 6 and 15 after taking azithromycin, which is typically associated with mild side effects in less than 1% of patients.

The symptoms appeared within 24 hours of the first dose and resolved slowly over 2-4 weeks, suggesting a potential genetic or environmental factor influencing the drug's effects on the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric manifestations associated with azithromycin in two brothers. Schiff, E., May, K., Goldstein, LH.[2021]

In a clinical trial involving 1,886 adults and 726 children, azithromycin was found to have a low incidence of side effects (4.35% in adults and 3.03% in children), primarily mild gastrointestinal issues like diarrhea and abdominal pain.

Laboratory abnormalities occurred in 7.75% of adults and 19.23% of children, but these were not severe and were transient, indicating that azithromycin is generally safe for treating bacterial infections across all age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical safety of azithromycin]. Higa, F., Saito, A.[2016]

Aztreonam (AZT) was found to be safe and effective in treating Gram-negative bacterial infections in 16 children, including conditions like pneumonia and meningitis.

The drug demonstrated good penetration into inflamed cerebrospinal fluid, making it effective for treating both acute purulent and viral meningitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic evaluations of aztreonam in children]. Meguro, H., Arimasu, O., Sugamata, K., et al.[2016]

Azithromycin is highly effective against a range of bacteria, including Staphylococcus aureus and Haemophilus influenzae, showing particularly strong activity against H. influenzae compared to other macrolides.

After oral administration, azithromycin is well-absorbed and distributed throughout the body, achieving higher concentrations in infected tissues due to its selective delivery by phagocytes, leading to successful treatment outcomes for respiratory infections with a convenient 3-day dosing regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and pharmacokinetic properties of azithromycin (Zithromac), a novel 15-membered ring macrolide antibacterial agent]. Matsunaga, T.[2019]

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]

Azithromycin is an effective broad-spectrum antibiotic with a long half-life and good tissue penetration, making it suitable for treating various infections, including respiratory and sexually transmitted infections.

While azithromycin has beneficial immunomodulatory effects for chronic respiratory diseases, it carries risks of serious side effects like cardiovascular arrhythmias and hearing loss, and there are concerns about macrolide resistance and drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing azithromycin. McMullan, BJ., Mostaghim, M.[2023]

Azithromycin extended-release (Zmax) is the first single-dose antibacterial approved in the US for treating mild to moderate acute bacterial sinusitis (ABS) and community-acquired pneumonia (CAP), demonstrating good tissue penetration and a broad spectrum of antibacterial activity.

In clinical trials, a single 2.0 g dose of azithromycin was as effective as longer regimens of levofloxacin and clarithromycin, suggesting it offers a convenient treatment option that may improve patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin extended release: a review of its use in the treatment of acute bacterial sinusitis and community-acquired pneumonia in the US. Swainston Harrison, T., Keam, SJ.[2018]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Control of a school outbreak of serogroup B meningococcal disease by chemoprophylaxis with azithromycin and ciprofloxacin]. [2013]

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

Increasing isolations of Neisseria meningitides serogroup A from blood and cerebrospinal fluid in Dhaka, Bangladesh, 1999-2006. [2009]

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

Azithromycin compared with rifampin for eradication of nasopharyngeal colonization by Neisseria meningitidis. [2019]

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

The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study. [2020]

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

The clinical features and long-term sequelae of invasive meningococcal disease in children. [2022]

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

Clinical toleration and safety of azithromycin. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Neuropsychiatric manifestations associated with azithromycin in two brothers. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

[Clinical safety of azithromycin]. [2016]

9. Japan pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic evaluations of aztreonam in children]. [2016]

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

[Pharmacological and pharmacokinetic properties of azithromycin (Zithromac), a novel 15-membered ring macrolide antibacterial agent]. [2019]

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

Azithromycin in lower respiratory tract infections. [2013]

12. Australia pubmed.ncbi.nlm.nih.gov

Prescribing azithromycin. [2023]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Azithromycin extended release: a review of its use in the treatment of acute bacterial sinusitis and community-acquired pneumonia in the US. [2018]