Azithromycin for Trachoma

(KETFO Trial)

Not currently recruiting at 1 trial location

Overseen By Hadley Burroughs, MSPH

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Disqualifiers: Non-consent

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: 12

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if more frequent doses of the antibiotic azithromycin can better eliminate trachoma, an eye infection that can lead to blindness, compared to the standard yearly treatment recommended by the World Health Organization (WHO). The study will compare different treatment groups, including those receiving annual treatments and others getting quarterly doses, with a particular focus on selected groups like children. Individuals living in communities where trachoma is prevalent and who are willing to participate might be suitable for this trial. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment can benefit more patients.

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

The trial information does not specify whether you need to stop taking your current medications.

What is the safety track record for azithromycin?

Research has shown that azithromycin, the treatment used in this study, is generally safe for people. It has been widely used to treat infections, including trachoma. Past studies demonstrated that administering azithromycin to many people at once for trachoma treatment was very effective, with reassuring safety results. Most people tolerated the treatment well, with very few experiencing serious side effects.

Common mild side effects include an upset stomach or diarrhea, but these usually resolve on their own. This treatment is part of the World Health Organization's (WHO) efforts to eliminate trachoma, supporting its safety when used correctly. Pfizer donates azithromycin worldwide for this purpose, highlighting its trusted use in health programs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Azithromycin is unique in the fight against trachoma because it offers the flexibility of different treatment strategies designed to maximize impact. Traditional treatments for trachoma generally involve mass antibiotic distribution to entire communities. However, researchers are excited about azithromycin because of its potential for more targeted interventions. This trial explores various strategies, including PCR infection-based and conjunctival photography-based approaches, which allow for targeted treatment of specific groups within the community. This could make treatment more efficient and effective, potentially reducing the prevalence of trachoma with fewer resources.

What evidence suggests that this trial's treatments could be effective for trachoma?

Research has shown that azithromycin effectively treats trachoma, an infectious eye disease. Studies have found that administering azithromycin to entire communities can significantly reduce trachoma rates, particularly in areas where the disease is prevalent. In one study, 63.3% of patients treated with azithromycin experienced improvement in their trachoma. This trial will compare different strategies for azithromycin distribution. One arm will follow the WHO-recommended approach of annual mass distribution to all residents, while other arms will explore more intensive treatments, such as quarterly treatments for specific groups. Overall, azithromycin is a proven treatment for trachoma and is frequently used in efforts to eliminate the disease in communities. ^{1 2 3 6 7}

Who Is on the Research Team?

Tom Lietman, MD

Principal Investigator

University of California, San Francisco

Hadley Burroughs, MSPH

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for everyone in certain communities where trachoma, an eye infection that can cause blindness, is common. People of all ages can get azithromycin annually as per WHO guidelines. Only those who don't agree to participate are excluded.

Inclusion Criteria

All individuals in all communities will be eligible for annual mass azithromycin distribution per WHO guidelines.

Exclusion Criteria

Those who do not consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Annual mass azithromycin distribution with additional quarterly targeted treatments based on trial arm

36 months

Annual visits for mass distribution, quarterly visits for targeted treatment

Follow-up

Participants are monitored for ocular chlamydia prevalence and other secondary outcomes

36 months

Annual assessments at 12, 24, and 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Azithromycin

Trial Overview

The study tests if giving out azithromycin more intensively and targeting specific areas works better for getting rid of trachoma than the current WHO method of handing it out once a year to everyone.

How Is the Trial Designed?

Group I: TI-based core group Experimental Treatment 1 Intervention

Annual mass azithromycin treatment plus quarterly treatment of a conjunctival photography-based cohort that would be a subset of the age-based core group

Group II: PCR infection-based core group Experimental Treatment 1 Intervention

Annual mass azithromycin treatment plus quarterly treatment of a PCR-based cohort that would be a subset of the age-based core group.

Group III: Age-based core group Experimental Treatment 1 Intervention

Annual mass azithromycin treatment of everyone plus quarterly treatment of children

Group IV: WHO-recommended Active Control 1 Intervention

Annual mass azithromycin distribution of all residents

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+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Bahir Dar University

Collaborator

Trials

10

Recruited

330,000+

Eyu-Ethiopia

Collaborator

Trials

1

Recruited

320,000+

Published Research Related to This Trial

Azithromycin 1.5% ophthalmic solution is effective in treating purulent bacterial conjunctivitis, showing similar clinical cure rates to tobramycin 0.3% over different treatment durations in a multicenter study involving both adults and children.

In cases of trachomatous conjunctivitis, a 3-day treatment with azithromycin 1.5% was as effective as a single oral dose of azithromycin, demonstrating its efficacy and good tolerability in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin 1.5% ophthalmic solution: in purulent bacterial or trachomatous conjunctivitis. Garnock-Jones, KP.[2021]

In a study involving approximately 120,000 individuals in Cameroon, azithromycin 1.5% eye drops significantly reduced the prevalence of active trachoma in children aged 1-9 years, from 24.0% before treatment to 2.8% one year after three annual treatment campaigns.

The treatment was well-tolerated with no serious adverse events reported, demonstrating both safety and efficacy in controlling trachoma in a highly endemic area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of azithromycin 1.5% eye drops for mass treatment of active trachoma in a highly endemic district in Cameroon. Bella, AL., Einterz, E., Huguet, P., et al.[2022]

In a cluster-randomized trial in Ethiopia, mass treatment with azithromycin for trachoma showed a low prevalence of adverse events, ranging from 4.9% to 7.0% in children aged 1-9 and 17.0% to 18.7% in individuals aged 10 and older.

The study indicated that adverse events were generally well tolerated and tended to cluster by household or village, suggesting that mass azithromycin distributions are safe in this community setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events after mass azithromycin treatments for trachoma in Ethiopia. Ayele, B., Gebre, T., House, JI., et al.[2021]

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]

After three years of mass azithromycin treatment in the Gurage zone, the prevalence of active trachoma among children aged 1 to 9 was found to be 22.8%, which is lower than the regional average of 33.2% in 2006, indicating some effectiveness of the treatment.

Despite the mass treatment, the prevalence of active trachoma remained high, suggesting that additional public health measures, such as improving water supply, sanitation, and hygiene practices, are necessary to effectively eliminate the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active trachoma two years after three rounds of azithromycin mass treatment in Cheha District Gurage Zone, Southern Ethiopia. Admassu, F., Bayu, S., Bejiga, A., et al.[2021]

In a study involving 48 Ethiopian communities, targeted azithromycin treatment for children aged 6 months to 5 years with ocular chlamydia did not significantly reduce the prevalence of infections compared to untreated communities, indicating that this approach may not be effective in hyperendemic areas.

The targeted treatment did not meet noninferiority criteria when compared to mass azithromycin distributions in older children (8-12 years), suggesting that broader treatment strategies may be necessary to effectively combat trachoma in these regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Antibiotics for Trachoma: A Cluster-Randomized Trial. Melo, JS., Aragie, S., Chernet, A., et al.[2022]

Azithromycin, given as a single oral dose, is both safe and effective for treating active trachoma in children, showing sustained high levels in the conjunctival tissue for up to 2 weeks after administration.

The prolonged presence of azithromycin in the eye tissue, above the minimum inhibitory concentration for Chlamydia trachomatis, supports its use as a suitable treatment for endemic trachoma, which is a major cause of preventable blindness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trachoma: a review. Tabbara, KF.[2019]

In a study involving 670 children with active trachoma, azithromycin 1.5% eye drops administered twice daily for 2 or 3 days were found to be as effective as the standard oral azithromycin treatment, with cure rates of 93.0% to 96.6%.

The eye drop treatment showed a low clinical re-emergence rate of 4.2% and no treatment-related adverse events, indicating it is a safe and effective alternative to oral medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of short duration azithromycin eye drops versus azithromycin single oral dose for the treatment of trachoma in children: a randomised, controlled, double-masked clinical trial. Cochereau, I., Goldschmidt, P., Goepogui, A., et al.[2022]

A single oral dose of azithromycin (20 mg/kg) was found to be effective in treating trachoma, with 78% of patients showing resolution of the disease after 26 weeks, compared to 72% with conventional treatment (topical tetracycline and erythromycin).

Azithromycin was well tolerated and offers a significant advantage as a systemic treatment that requires only one dose, making it a practical option for trachoma control in endemic areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of single-dose azithromycin in treatment of trachoma. Bailey, RL., Arullendran, P., Whittle, HC., et al.[2019]

In a study conducted in northern Ethiopia with 24 subdistricts, both annual and twice-yearly distributions of azithromycin significantly reduced the prevalence of ocular chlamydial infection in children aged 0-9 years, with rates dropping from around 41.9% and 38.3% at baseline to 1.9% and 3.2% respectively after 42 months.

Although the overall prevalence of infection was similar between the two treatment groups at the end of the study, the twice-yearly treatment group showed a trend towards faster elimination of infection, suggesting that more frequent dosing may lead to quicker results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial. Gebre, T., Ayele, B., Zerihun, M., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8710348/

Effectiveness of azithromycin mass drug administration on ...

The effectiveness of azithromycin MDA on reducing trachoma is related to local epidemiology and the baseline TF prevalence. Additionally, the effects are also ...

2.

bmjopen.bmj.com

bmjopen.bmj.com/content/15/2/e087170

Annual versus biannual azithromycin mass drug ...

Mass azithromycin distributions have demonstrated high efficacy in treating trachoma; however, regions with the most severe disease burden have struggled to ...

3.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2795556

Effect of Biannual Mass Azithromycin Distributions to ...

The present study assessed prespecified trachoma outcomes from the smaller trial in Niger, which was a parallel-group, placebo-controlled ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00286026

NCT00286026 | Azithromycin in Control of Trachoma II

If the prevalence of clinical trachoma is over 20% in children 10 and under, everyone in the village will be treated with oral azithromycin.

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0161642096306052

Single-dose Azithromycin in the Treatment of Trachoma

Results: Trachoma resolved in 17 (63.3%) patients who received azithromycin compared with 19 (65.4%) who were treated with tetracycline ointment. There were no ...

6.

who.int

who.int/news/item/23-06-2022-trachoma-elimination--millions-more-to-benefit-from-donated-azithromycin

Trachoma elimination: millions more to benefit from ...

Pfizer's Zithromax® donation is a critical part of SAFE, and is managed by the International Trachoma Initiative at the Task Force for ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39719287/

the stronger SAFE trial protocol

The aim of stronger SAFE is to evaluate the impact of a novel package of interventions to strengthen the A, F and E of SAFE on the prevalence of ocular Ct and ...