Impact of Two Alternative Dosing Strategies for Trachoma Control in Niger

NCT00618449 | Completed Phase 4 Results

• 2 other identifiers: H1079-319325R01AI048789
• Study Type: interventional
• Target: 1,139
• Locations: 2 countries
• Sites: 2

Brief Summary

Trachoma is a disease of poverty, which in the hyperendemic areas affects all individuals by the time they are two years old. Active disease is concentrated in children and occurs sporadically in adults. Infection is more widespread. It is anticipated that 25% of the children will be blinded by this disease if they live to be 60 years of age. The blindness rates are higher in women, presumably because of their closer contact with children who can infect them and add to damage from infections the women had while young. This proposal is to better define how azithromycin in community-based treatment can be used to eliminate blinding trachoma. We will also take the opportunity to join these field studies with genetic epidemiologic studies to better understand the dynamic epidemiology of Chlamydia trachomatis infection in a trachoma endemic area. The empiric data generated from the treatment/follow-up studies, together with the information on sources and spread patterns from genetic epidemiology will be used to generate more robust models to guide future treatment/re-treatment protocols. We propose to conduct a randomized, community based trial in the Maradi region of Niger to test the hypothesis that two community wide azithromycin treatments, spaced one month apart, are significantly more effective in reducing ocular C. trachomatis infection and trachoma at one year compared to a single mass azithromycin treatment.

Conditions

Trachoma; Chlamydia Trachomatis

Keywords

Trachoma; Chlamydia trachomatis

Outcome Measures

Primary Outcomes (1)

• Infection With Chlamydia Trachomatis Diagnosed by Use of NAATs [Nucleic Acid Amplification Test]

  1-year post-treatment

Study Arms (2)

Arm 2

EXPERIMENTAL

Subjects residing in villages assigned to treatment arm 2 will receive a clinical evaluation for trachoma and provide a swab specimen of conjunctivae of the R eye at enrollment (Day 0), as well as receive an initial treatment with 1 gm oral dose of Azithromycin; receive a second 1 gm oral dose of Azithromycin at Day 30; be re-screened (clinical evaluation and swab specimen of R eye collected) at Day 60 and Day 360.

Drug: Azithromcyin

Arm 1

ACTIVE COMPARATOR

Subjects residing in villages assigned to treatment arm 1 will receive a clinical evaluation for trachoma and provide a swab specimen of conjunctivae of the R eye at enrollment (Day 0); be treated at Day 30 with the WHO standard of care for trachoma - 1 gm oral dose of Azithromycin; be re-screened (clinical evaluation and swab specimen of R eye collected) at Day 60 and Day 360.

Drug: Azithromycin

Interventions

Azithromcyin DRUG

1 gm Azithromycin orally, provided as four 250 mg tablets for adults; pediatric suspension will be provided to children \> 1 year old (20 mg/kg body weight) to a maximal dose of 500 mg - Given 30 days apart; at Day 0 \& Day 30 for a total of 2 doses.

Arm 2

Azithromycin DRUG

1 gm Azithromycin orally, provided as four 250 mg tablets for adults; pediatric suspension will be provided to children \> 1 year old (20 mg/kg body weight) to a maximal dose of 500 mg - Given at Day 30 for a total of 1 dose.

Arm 1

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study the subject must live in one of the villages selected for this study.

You may not qualify if:

• history of allergy to ANY macrolide antibiotic
• severe nausea or diarrhea after the first dose of azithromycin
• inability to tolerate oral therapy
• pre-existing serious illness

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Chlamydia Research Laboratory

San Francisco, California, 94110, United States

Location

Programme National de Lutte Contre la Cécité

Niamey, Niger

Location

Related Publications (20)

• Thylefors B, Negrel AD, Pararajasegaram R, Dadzie KY. Global data on blindness. Bull World Health Organ. 1995;73(1):115-21.

  PMID: 7704921 BACKGROUND

• Dawson CR, Jones BR, Tarizzo ML. A Guide to Trachoma Control. Geneva: World Health Organization; 1981.

  BACKGROUND

• Dawson CR, Schachter J. Strategies for treatment and control of blinding trachoma: cost-effectiveness of topical or systemic antibiotics. Rev Infect Dis. 1985 Nov-Dec;7(6):768-73. doi: 10.1093/clinids/7.6.768.

  PMID: 4070912 BACKGROUND

• Thylefors B. Development of trachoma control programs and the involvement of national resources. Rev Infect Dis. 1985 Nov-Dec;7(6):774-6. doi: 10.1093/clinids/7.6.774.

  PMID: 4070913 BACKGROUND

• World Health Organization. Future Approaches to Trachoma Control. Report of a global scientific meeting. 17 - 20 June 1996.

  BACKGROUND

• Dawson CR, Daghfous T, Hoshiwara I, Ramdhane K, Kamoun M, Yoneda C, Schachter J. Trachoma therapy with topical tetracycline and oral erythromycin: a comparative trial. Bull World Health Organ. 1982;60(3):347-55.

  PMID: 6754118 BACKGROUND

• Malaty R, Zaki S, Said ME, Vastine DW, Dawson DW, Schachter J. Extraocular infections in children in areas with endemic trachoma. J Infect Dis. 1981 Jun;143(6):853. doi: 10.1093/infdis/143.6.853. No abstract available.

  PMID: 7252266 BACKGROUND

• West S, Munoz B, Bobo L, Quinn TC, Mkocha H, Lynch M, Mmbaga BB, Viscidi R. Nonocular Chlamydia infection and risk of ocular reinfection after mass treatment in a trachoma hyperendemic area. Invest Ophthalmol Vis Sci. 1993 Oct;34(11):3194-8.

  PMID: 8407229 BACKGROUND

• Grayston JT, Wang S. New knowledge of chlamydiae and the diseases they cause. J Infect Dis. 1975 Jul;132(1):87-105. doi: 10.1093/infdis/132.1.87.

  PMID: 1097546 BACKGROUND

• Treharne JD. The community epidemiology of trachoma. Rev Infect Dis. 1985 Nov-Dec;7(6):760-4. doi: 10.1093/clinids/7.6.760.

  PMID: 4070910 BACKGROUND

• Katz J, Zeger SL, Tielsch JM. Village and household clustering of xerophthalmia and trachoma. Int J Epidemiol. 1988 Dec;17(4):865-9. doi: 10.1093/ije/17.4.865.

  PMID: 3265700 BACKGROUND

• Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2002 May 10;51(RR-6):1-78.

  PMID: 12184549 BACKGROUND

• Martin DH, Mroczkowski TF, Dalu ZA, McCarty J, Jones RB, Hopkins SJ, Johnson RB. A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group. N Engl J Med. 1992 Sep 24;327(13):921-5. doi: 10.1056/NEJM199209243271304.

  PMID: 1325036 BACKGROUND

• Adair CD, Gunter M, Stovall TG, McElroy G, Veille JC, Ernest JM. Chlamydia in pregnancy: a randomized trial of azithromycin and erythromycin. Obstet Gynecol. 1998 Feb;91(2):165-8. doi: 10.1016/s0029-7844(97)00586-3.

  PMID: 9469269 BACKGROUND

• Bailey RL, Arullendran P, Whittle HC, Mabey DC. Randomised controlled trial of single-dose azithromycin in treatment of trachoma. Lancet. 1993 Aug 21;342(8869):453-6. doi: 10.1016/0140-6736(93)91591-9.

  PMID: 8102427 BACKGROUND

• Schachter J, Hook EW, Martin DH, Willis D, Fine P, Fuller D, Jordan J, Janda WM, Chernesky M. Confirming positive results of nucleic acid amplification tests (NAATs) for Chlamydia trachomatis: all NAATs are not created equal. J Clin Microbiol. 2005 Mar;43(3):1372-3. doi: 10.1128/JCM.43.3.1372-1373.2005.

  PMID: 15750110 BACKGROUND

• Schachter J, Chernesky MA, Willis DE, Fine PM, Martin DH, Fuller D, Jordan JA, Janda W, Hook EW 3rd. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: results from a multicenter evaluation of the APTIMA assays for both infections. Sex Transm Dis. 2005 Dec;32(12):725-8. doi: 10.1097/01.olq.0000190092.59482.96.

  PMID: 16314767 BACKGROUND

• Dawson CR, Jones DB, Kaufman HE, Barron BA, Hauck WW, Wilhelmus KR. Design and organization of the herpetic eye disease study (HEDS). Curr Eye Res. 1991;10 Suppl:105-10. doi: 10.3109/02713689109020365.

  PMID: 1864086 BACKGROUND

• Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med. 1998 Jul 30;339(5):300-6. doi: 10.1056/NEJM199807303390503.

  PMID: 9696640 BACKGROUND

• Stephens RS, Kalman S, Lammel C, Fan J, Marathe R, Aravind L, Mitchell W, Olinger L, Tatusov RL, Zhao Q, Koonin EV, Davis RW. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science. 1998 Oct 23;282(5389):754-9. doi: 10.1126/science.282.5389.754.

  PMID: 9784136 BACKGROUND

Related Links

• Chlamydia genome

MeSH Terms

Conditions

Trachoma

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Conjunctivitis, Bacterial; Eye Infections, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Chlamydia Infections; Chlamydiaceae Infections; Gram-Negative Bacterial Infections; Eye Infections; Conjunctivitis; Conjunctival Diseases; Eye Diseases; Corneal Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Limitations and Caveats

Prevalence of infection in communities was less than predicted, as was return of infection post-treatment, thus hypothesis could not be evaluated.

Results Point of Contact

• Title: Julius Schachter, PhD / Emeritus Professor of Laboratory Medicine
• Organization: University of California, San Francisco

Julius.Schachter@ucsf.edu

+1 (415) 824-5115

Study Officials

• Julius Schachter, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Abdou Amza, MD

  Programme National de Lutte Contre la Cécité

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2008
• First Posted: February 20, 2008
• Study Start: January 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: August 1, 2009
• Last Updated: May 8, 2012
• Results First Posted: May 8, 2012

Record last verified: 2012-04

Locations

NI (1); US (1)