Azithromycin for MAC Infection

Overseen By Jennifer Hoffmann

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Disqualifiers: Pregnancy, HIV, Transplant, 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 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

To assess the early bactericidal activity of Azithromycin 250mg by mouth daily over the first 14 days of treatment for Mycobacterium avium complex (MAC) lung disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Azithromycin for treating MAC infection?

Azithromycin is effective in treating various bacterial infections, including community-acquired pneumonia and acute bacterial sinusitis, due to its ability to penetrate tissues and target bacteria effectively. It is also a key component in treating Mycobacterium avium complex lung disease, suggesting its potential effectiveness for MAC infections. ^{1 2 3 4 5}

Is azithromycin generally safe for humans?

Azithromycin is generally considered safe for humans, with common side effects like diarrhea and stomach pain being mild or moderate. Serious side effects are rare, but can include heart rhythm issues and liver problems. It is well tolerated even with other illnesses and medications. ^{6 7 8 9 10}

How is the drug azithromycin unique in treating MAC infection?

Azithromycin is unique in treating MAC infection because it can be administered in a convenient weekly dose, which may improve patient compliance compared to daily regimens. It also achieves high and prolonged levels inside cells, potentially offering effective protection against MAC in individuals with advanced AIDS. ^{1 3 5 11 12}

Research Team

Elisa Ignatius, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults over 18 with MAC lung disease, as defined by ATS/IDSA criteria. Participants must have had a positive test for M. avium complex in the last 6 months and be able to produce a sputum sample. They cannot join if they've had an organ transplant, are allergic to azithromycin, were treated for MAC recently, are pregnant or have HIV with CD4 <350.

Inclusion Criteria

Isolation of M. avium intracellulare complex from a respiratory specimen in the preceding 6 months

Signed informed consent by the subject

My doctor plans to treat me for MAC lung disease.

Exclusion Criteria

Pregnancy

I have had an organ or bone marrow transplant.

Has any other condition that, in the opinion of the PI, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Azithromycin 250mg daily for the first 14 days as monotherapy

2 weeks

Daily visits for monitoring

Standard Multi-drug Therapy

Participants receive guideline-based standard multi-drug therapy for Mycobacterium avium lung disease

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Azithromycin

Trial Overview The study tests Azithromycin's effectiveness against Mycobacterium avium complex (MAC) infection over the first two weeks of treatment. Patients will take 250mg of Azithromycin orally every day.

Participant Groups

Group I: 14 Day Azithromycin Monotherapy Experimental Treatment 1 Intervention

For the first 14 days of therapy, participants will receive Azithromycin 250mg PO daily as monotherapy. Beyond day 14, all participants will receive guideline-based standard multi-drug therapy for Mycobacterium avium lung disease, as dictated by the physicians treating the participants.

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 University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

American College of Chest Physicians

Collaborator

Trials

10

Recruited

2,200+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

CHEST Foundation

Collaborator

Trials

4

Recruited

190+

Findings from Research

Azithromycin (AZM) demonstrated strong antibacterial activity against various pathogens, with a high efficacy rate of 94.7% in treating infections in 76 pediatric patients, including pneumonia and bronchitis.

The drug has a long elimination half-life of approximately 28.1 to 46.1 hours, and while some mild laboratory abnormalities were noted, they were clinically insignificant, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical evaluation of azithromycin using fine granules or capsules in the pediatric patients]. Toyonaga, Y., Ishihara, T., Nakamura, H.[2016]

Azithromycin extended release (Zmax) is a single-dose formulation approved for treating community-acquired pneumonia and acute bacterial sinusitis, utilizing sustained-release microspheres to minimize gastrointestinal side effects.

The drug's unique sustained release mechanism allows for a higher dose to be administered effectively, targeting the lower gastrointestinal tract and leveraging its long half-life for effective single-dose therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose azithromycin microsphere formulation: a novel delivery system for antibiotics. Amrol, D.[2019]

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]

In a study involving 221 patients with Mycobacterium avium complex lung disease (MAC-LD), it was found that the peak plasma concentration (Cmax) of azithromycin (AZM) was significantly lower in patients receiving daily therapy compared to those on an intermittent regimen, suggesting that the current daily dosing may be suboptimal for effective treatment.

Higher AZM Cmax levels were associated with better microbiological responses in patients on a daily regimen for MAC-LD, indicating that adjusting the dosing strategy could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease. Jeong, BH., Jeon, K., Park, HY., et al.[2020]

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 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]

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]

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 generally considered a safe medication, with serious side effects like angioedema and cholestatic jaundice occurring in less than 1% of patients.

However, this report highlights a rare but severe case of dilated cardiomyopathy and significant liver toxicity leading to hepatic encephalopathy in a patient taking Azithromycin, suggesting that even commonly used medications can have unexpected serious effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy. Das, BK.[2021]

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]

A large trial is underway comparing the effectiveness of weekly azithromycin (1200 mg) to daily rifabutin (300 mg) for preventing Mycobacterium avium complex (MAC) disease in individuals with advanced AIDS, aiming to find a more convenient and cost-effective option.

Azithromycin has shown promise due to its high and prolonged intracellular levels, which may offer equivalent or better protection against MAC compared to the currently approved rifabutin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin in the prophylaxis of opportunistic infections in AIDS. McCutchan, JA.[2017]

In a study involving 92 patients with pulmonary Mycobacterium avium complex (MAC) disease, multidrug regimens containing azithromycin were effective, with treatment success rates of 59% for daily dosing, 55% for thrice-weekly dosing with daily companions, and 65% for thrice-weekly dosing with thrice-weekly companions.

All treatment regimens, which included rifabutin or rifampin and ethambutol, showed no significant differences in outcomes, indicating that both daily and thrice-weekly azithromycin regimens are viable options for treating MAC lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin-containing regimens for treatment of Mycobacterium avium complex lung disease. Griffith, DE., Brown, BA., Girard, WM., et al.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and clinical evaluation of azithromycin using fine granules or capsules in the pediatric patients]. [2016]

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

Single-dose azithromycin microsphere formulation: a novel delivery system for antibiotics. [2019]

3. 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]

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

Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease. [2020]

5. Japan pubmed.ncbi.nlm.nih.gov

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

6. Australia pubmed.ncbi.nlm.nih.gov

Prescribing azithromycin. [2023]

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

Single-dose azithromycin for respiratory tract infections. [2007]

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

Clinical toleration and safety of azithromycin. [2022]

9. India pubmed.ncbi.nlm.nih.gov

Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy. [2021]

10. India pubmed.ncbi.nlm.nih.gov

Evaluation of safety and efficacy of azithromycin in lower respiratory tract infections (LRTI) [2020]

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

Azithromycin in the prophylaxis of opportunistic infections in AIDS. [2017]

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

Azithromycin-containing regimens for treatment of Mycobacterium avium complex lung disease. [2022]