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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how effectively Azithromycin (also known as Zithromax or Zmax) reduces bacteria in individuals with Mycobacterium avium complex (MAC) lung disease during the first two weeks of treatment. Participants will take Azithromycin daily for 14 days before transitioning to standard multi-drug therapy. Individuals who have had a confirmed MAC lung infection in the last six months and can produce a sputum sample may be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that azithromycin has been tested for safety in treating Mycobacterium avium complex (MAC) lung disease. In some studies, participants taking higher doses, such as 600 mg daily, experienced side effects. Common side effects included stomach issues in 76% of participants and hearing changes in 41%. However, this trial uses a lower dose of 250 mg daily, which might lead to fewer side effects.

The FDA has already approved azithromycin to prevent MAC disease, suggesting it is considered safe for similar uses. This approval can provide some confidence in its safety, although individual reactions may vary.

Overall, while higher doses have been linked to side effects, using a lower dose in this trial could be gentler on the body. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard multi-drug regimens for Mycobacterium avium complex (MAC) lung infections, which often include a combination of drugs like clarithromycin, rifampin, and ethambutol, azithromycin offers a simpler approach as a monotherapy for the initial phase of treatment. Researchers are excited about azithromycin because it could potentially simplify treatment by reducing the number of medications a patient needs to take initially, which may improve adherence and reduce side effects. Additionally, starting with azithromycin alone before moving to a multi-drug regimen could help in assessing its direct effectiveness, potentially leading to more tailored and efficient treatment strategies for MAC infections.

What evidence suggests that Azithromycin might be an effective treatment for MAC lung disease?

Studies have shown that azithromycin is a preferred treatment for Mycobacterium avium complex (MAC) lung disease. Research indicates that azithromycin can be safe and effective, particularly for patients who struggle with other standard treatments like clarithromycin. In past studies, about 57% of patients achieved successful treatment for MAC lung disease with similar regimens. This trial will evaluate azithromycin as a monotherapy for the first 14 days, after which all participants will receive guideline-based standard multi-drug therapy for MAC lung disease. This approach suggests that azithromycin might help fight the infection, especially for those who can't tolerate other drugs. Overall, azithromycin is part of the recommended treatment guidelines for MAC lung disease. ^{1 5 6 7 8}

Who Is on the Research Team?

Elisa Ignatius, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 (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]

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]

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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10581154/

Treatment outcomes and relapse in patients with ... The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain.

2. academic.oup.com academic.oup.com/cid/article/65/7/1077/3861185

Treatment Outcomes of Mycobacterium avium Complex Lung ... In those studies, the treatment success rate was 56.8% (95% CI, 46.0%–66.8%). The treatment success rate for the patients with a history of anti-TB or anti–MAC- ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2212534520301374

Resumption/efficacy and safety of an azithromycin ... AZM may be safe and effective for patients with MAC lung disease who have difficulty tolerating CLR. In patients who experienced AEs possibly caused by CLR, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00599079

Azithromycin in the Treatment of M. Avium Complex Lung ... abscessus lung disease. Detailed Description. To study the safety and efficacy of azithromycin in combination treatment for M. abscessus and MAC lung disease.

5. journals.asm.org journals.asm.org/doi/10.1128/spectrum.00218-24

Minimum inhibitory concentrations of azithromycin in clinical ... The latest guidelines include azithromycin as a preferred regimen for treating Mycobacterium avium complex (MAC) pulmonary disease.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8922790/

Azithromycin activity against Mycobacterium avium ... Although most patients continued to receive 600 mg of azithromycin/d, the high incidence of gastrointestinal side effects (76%) and altered hearing (41%) ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/050693s017,050730s026lbl.pdf

ZITHROMAX - accessdata.fda.gov Azithromycin has demonstrated in vitro activity against Mycobacterium avium complex (MAC) ... Prophylaxis of Disseminated Mycobacterium avium complex (MAC) Disease.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4808200/

Azithromycin Dose To Maximize Efficacy and Suppress ... Currently, azithromycin is administered at doses of 500 to 600 mg in combination therapy, based on very limited clinical data, and in the treatment of cavitary ...