Azithromycin for Trachoma

(KETFO Trial)

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

320000 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators propose a cluster-randomized clinical trial to determine whether an intensive, targeted azithromycin distribution strategy is effective for elimination of trachoma at the kebele level compared to the World Health Organization (WHO) recommendation of annual azithromycin distribution.

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 data supports the effectiveness of the drug Azithromycin for treating trachoma?

Research shows that a single oral dose of Azithromycin is effective in treating trachoma, with 78% of patients showing improvement, similar to conventional treatments. Additionally, Azithromycin has been used successfully in mass treatments to reduce trachoma infections in communities. ^{1 2 3 4 5}

Is azithromycin safe for humans?

Azithromycin is generally safe for humans, with side effects like diarrhea and abdominal pain occurring in about 12% of patients, mostly mild or moderate. In mass treatments for trachoma, adverse events were reported in 4.9% to 18.7% of people, but the treatment was well tolerated. ^{2 6 7 8 9}

How is the drug Azithromycin unique in treating trachoma?

Azithromycin is unique for trachoma treatment because it can be administered as a 1.5% eye drop solution, which is effective with a short 3-day treatment, compared to longer courses of other antibiotics. This makes it more convenient and potentially better tolerated, especially for children. ^{1 2 3 4 10}

Research Team

Hadley Burroughs, MSPH

Principal Investigator

University of California, San Francisco

Tom Lietman, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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 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]

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]

References

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

Active trachoma two years after three rounds of azithromycin mass treatment in Cheha District Gurage Zone, Southern Ethiopia. [2021]

2. England 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. [2022]

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

Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial. [2021]

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

Targeted Antibiotics for Trachoma: A Cluster-Randomized Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of single-dose azithromycin in treatment of trachoma. [2019]

6. England 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Trachoma: a review. [2019]

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

Adverse events after mass azithromycin treatments for trachoma in Ethiopia. [2021]

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

Clinical toleration and safety of azithromycin. [2022]

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

Azithromycin 1.5% ophthalmic solution: in purulent bacterial or trachomatous conjunctivitis. [2021]