Azithromycin for Trachoma

(KETFO Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Tom Lietman, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of California, San Francisco

Disqualifiers: Non-consent

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

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}

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.

Trial 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 (Macrolide Antibiotic)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UCSF Proctor Foundation San Francisco, CA

Who Is Running the Clinical Trial?

University of California, San Francisco Lead Sponsor

National Eye Institute (NEI) Collaborator

Bahir Dar University Collaborator

Eyu-Ethiopia Collaborator

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] Azithromycin mass distribution was given to residents of Gurage zone Cheha district in 2004, 2005 and 2006 for three consecutive years with more than 90% coverage. The effect of treatment in the study community was not yet determined. The present study was therefore designed to assess the effect of azithromycin on the prevalence of active trachoma two years after three rounds of mass treatment of the community at Cheha district, Gurage zone.

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] Efficacy and safety of a short-duration treatment of azithromycin 1.5% eye drops versus oral azithromycin to treat active trachoma.

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] In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains.

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

Targeted Antibiotics for Trachoma: A Cluster-Randomized Trial. [2022] Current guidelines recommend community-wide mass azithromycin for trachoma, but a targeted treatment strategy could reduce the volume of antibiotics required.

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

Randomised controlled trial of single-dose azithromycin in treatment of trachoma. [2019] Blindness due to trachoma is a serious public health issue world wide. The currently recommended treatment of active trachoma with repeated doses of tetracycline eye ointment has many disadvantages. The new azalide antibiotic azithromycin is effective as a single oral dose in the chemotherapy of genital Chlamydia trachomatis infections, and we have assessed its efficacy for trachoma treatment. We carried out a randomised single-blind comparison of azithromycin (a single oral dose of 20 mg/kg) with conventional treatment (6 weeks of topical tetracycline plus erythromycin for severe cases) in two villages with endemic trachoma in The Gambia. The patients were followed up for 26 weeks from the start of treatment by an observer unaware of treatment allocation. By 6 months' follow-up, trachoma had resolved in 76 (78%) of 97 subjects who received azithromycin compared with 70 (72%) of 97 who were treated conventionally (95% CI for difference -6% to 18%). Compliance with both treatments was good, but that for conventional treatment could probably not be achieved outside the research setting. There were no significant differences in treatment effect, baseline characteristics, or re-emergent disease between the treatment groups. Azithromycin was well tolerated. As a systemic treatment effective in a single dose it has important potential for trachoma control.

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] To evaluate the effectiveness and safety of azithromycin 1.5% eye drops under field conditions to reduce active trachoma in a highly endemic district in Cameroon. This is a follow-up of an initial report published in 2010.

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

Trachoma: a review. [2019] Trachoma is a leading cause of preventable blindness worldwide. The disease is caused by an intracellular epithelial gram-negative bacterium, Chlamydia trachomatis. The presence of children, overcrowding, and the lack of water in the household are factors that predispose to the transmission of the disease. The disease may remain asymptomatic but some patients many complain of redness, irritation, and ocular discharge. The principal initial clinical manifestation is a follicular conjunctivitis that may lead to conjunctival scarring, entropion, trichiasis, corneal thinning, and ulceration. Some patients develop corneal scars that lead to loss of vision. Despite the remarkable progress in our understanding of Chlamydial infections, the basic mechanisms involved in tissue damage and scarring remain to be elucidated. There are several effective therapeutic modalities for trachoma. Azithromycin oral single dose was found to be safe and effective in children with active trachoma. Conjunctival biopsy specimens obtained from adult patients receiving a single oral dose of azithromycin showed sustained high levels of azithromycin (above MIC of chlamydia) for up to 2 weeks after intake. These prolonged high levels of azithromycin in the conjunctival tissue following a single oral dose makes the drug suitable for the treatment of endemic trachoma.

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

Adverse events after mass azithromycin treatments for trachoma in Ethiopia. [2021] During a cluster-randomized clinical trial for trachoma in Ethiopia, two rounds of adverse event surveillance were performed in a random sample of communities after community-wide mass azithromycin treatment. The prevalence of any reported adverse event ranged from 4.9% to 7.0% in children 1-9 years of age and from 17.0% to 18.7% in persons ≥ 10 years of age. Adverse events appeared to cluster by household and perhaps by village. Mass azithromycin distributions were well tolerated in this setting.

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

Clinical toleration and safety of azithromycin. [2022] The toleration and safety profile of the azalide antibiotic, azithromycin, has been assessed in 3,995 patients aged 2-94 (mean, 36) years, comprising 1,644 females and 2,351 males. Patients with infections of the respiratory tract or skin/skin structure received 1.5 g azithromycin over 5 days; patients with urethritis/cervicitis caused by Chlamydia were treated with 1 g as a single dose. Assessments of side effects and laboratory safety test abnormalities were made pretreatment and approximately 7-14 and 30 days after the start of therapy. Twelve standard antibiotics have been used for comparison. Overall, side effects were recorded in 12.0% of patients, significantly less (p less than 0.05) than with comparative drugs (14.2%). The most common side effects were diarrhea (3.6%), abdominal pain (2.5%), and other gastrointestinal symptoms. Ninety-three percent of side effects were classed as mild or moderate, and only 0.7% of patients withdrew from treatment, significantly less (p less than 0.001) than with comparative agents (2.6%). The frequency of side effects was not affected by patient age. Azithromycin had no marked or consistent effect on laboratory safety parameters. Treatment-related laboratory abnormalities were rare, the most common being transient increases of ALT and AST in 1.7% and 1.5% of patients, respectively. Specific tests revealed no neurologic, audiometric, or ophthalmologic abnormalities, or evidence of phospholipidosis. There were no pharmacokinetic interactions observed with theophylline, warfarin, cimetidine, carbamazepine, or methylprednisolone, but coadministration with food altered the absorption of the drug. Coadministration with antacids decreased the peak serum concentration of azithromycin, but did not affect its overall absorption. Azithromycin was well tolerated in the presence of a wide variety of concurrent illnesses and medications.

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

Azithromycin 1.5% ophthalmic solution: in purulent bacterial or trachomatous conjunctivitis. [2021] The second-generation macrolide azithromycin is available as a 1.5% ophthalmic solution for use in the treatment of bacterial or trachomatous conjunctivitis. This article reviews the pharmacological properties of azithromycin 1.5% ophthalmic solution and its clinical efficacy and tolerability in patients with purulent bacterial conjunctivitis or trachomatous conjunctivitis caused by Chlamydia trachomatis. Azithromycin 1.5% ophthalmic solution had good in vitro activity against Haemophilus influenzae and C. trachomatis, and achieved good concentrations in tear samples from healthy volunteers. Azithromycin 1.5% ophthalmic solution for 3 days (1 drop twice daily) was noninferior to tobramycin 0.3% ophthalmic solution for 7 days (1 drop every 2 hours) in paediatric and adult patients with purulent bacterial conjunctivitis, with regard to clinical cure and bacteriological resolution on day 9, in a randomized, investigator-masked, multicentre study. In children with trachomatous inflammation, 3-day treatment with azithromycin 1.5% ophthalmic solution was noninferior to a single dose of azithromycin oral suspension, with regard to clinical cure rate in the worst eye at 60 days, in a randomized, double-masked, multicentre study. Azithromycin 1.5% ophthalmic solution was well tolerated in patients with bacterial or trachomatous conjunctivitis. Most events were of mild to moderate severity.