Partnership for Rapid Elimination of Trachoma

NCT ID: NCT00792922

Last Updated: 2017-07-18

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-05-31

Study Completion Date

2014-06-30

Brief Summary

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Trachoma, an ocular infection caused by C. trachomatis, is the second leading infectious cause of blindness worldwide. Years of repeated infection with C. trachomatis cause the eyelid to scar and contract and ultimately to rotate inward such that the eyelashes rub against the eyeball and abrade the cornea (trichiasis). The World Health Organization (WHO) has endorsed a multi-faceted strategy to combat trachoma, which includes the use of antibiotic treatment to reduce the community pool of infection with C. trachomatis. The objective of this study is to conduct a randomized, community-based trial in three countries (Niger, Tanzania and The Gambia), representing different baseline endemicities, of alternative coverages and frequencies of administration of mass antibiotic treatment as well as to determine the cost-effectiveness of these different strategies from a program perspective.

Detailed Description

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A randomized, 2x2 factorial designed trial will be implemented in each of the three countries. Communities will be randomized to two different coverage targets (80%-89% versus ≥90%) for three years of mass treatment.

In The Gambia and Tanzania, communities will be further randomized to yearly mass treatment versus mass treatment at baseline followed by yearly mass treatment only if trachoma prevalence in sentinel children is greater than 5%. The communities will continue to be followed and treatment will resume if trachoma prevalence is found to be 20% or greater at the 12 or 18 month surveys.

In Niger, communities will be randomized to the different coverage levels for annual mass azithromycin distribution and further randomized to biannual treatment at the two coverage targets for children ages twelve or younger.

Cross-sectional rates of trachoma and infection will be determined by examining sentinel children, age five years or younger, randomly selected from each community based on a community census. The census will be updated each year, and villages will be monitored at baseline, 6, 12, 18, 24, 30, and 36 months for infection and clinical disease.

The three-year study is in accord with the WHO guidelines which recommend three years of annual mass treatment followed by a re-survey to determine need for further treatment. The investigators will evaluate the efficacy of guiding further mass treatment according to a laboratory test for Chlamydia or WHO guidelines. Where investigators estimate communities have infection rates less than 5% in sentinel children, or trachomatous inflammation (TF) ( rates less than 5%, the community will be "graduated" from further mass treatment and followed for up to three years to look for evidence of re-emergent infection and disease. If rates of infection are found to be 20% or more return at the 12 or 18 month survey, mass treatment will be re-initiated.

Conditions

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Trachoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

The study was a factorial study model to begin with in all 3 countries (Niger,Tanzania and Gambia) but because we never stopped treatment in Tanzania and Niger site.Hence the study design was collapsed to a simple design in Tanzania and Niger.The study model was kept as a factorial design for the Gambia site.

Protocol Enrollment refers to the number of communities, not the number of participants enrolled.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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≥90% coverage with azithromycin target

Selected communities will receive mass treatment annually for three years.

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Comparison of community coverage rate

80%-89% coverage with azithromycin target

Selected communities will receive mass treatment annually for three years.

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Comparison of community coverage rate

≥90% coverage with azithromycin , treatment based

Treatment to be administered at baseline then continued yearly if trachoma prevalence is greater than 5%

In Niger, treatment will be every 6-months for children ages twelve and under.

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is \>5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months.

80%-89% coverage with azithromycin : treatment based

Treatment to be administered at baseline then continued yearly if trachoma prevalence is greater than 5%

In Niger, treatment will be every 6-months for children ages twelve and under.

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is \>5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months.

Interventions

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Azithromycin

Comparison of community coverage rate

Intervention Type DRUG

Azithromycin

Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is \>5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months.

Intervention Type DRUG

Other Intervention Names

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Zithromax Zithromax

Eligibility Criteria

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Inclusion Criteria

* Communities are located in the target districts and accessible by vehicle
* The community leaders consent to have the community enrolled
* Rapid assessment and/or available data suggest trachoma rates are higher than 20% in the community.
* The community size is \<5,000 persons or \>250 persons.


* The child is age 5 years or younger
* The child must be a resident in an eligible, sample community (defined as either living in the community since birth, or moved in with parents or guardians).
* The child must not have an ocular condition that would preclude grading trachoma or taking an ocular specimen.
* The child must be willing to have a swab taken as part of being a sentinel child (this is critical for The Gambia and Tanzania, as each swab result counts towards meeting the stopping rule)
* The child must have an identifiable guardian capable of providing consent to participate.
Maximum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sheila West, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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UCSF Proctor Foundation

San Francisco, California, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

London School of Hygiene and Tropical Medicine

London, , United Kingdom

Site Status

Countries

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United States United Kingdom

References

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Oldenburg CE, Amza A, Cooley G, Kadri B, Nassirou B, Arnold BF, Rosenthal PJ, O'Brien KS, West SK, Bailey RL, Porco TC, Keenan JD, Lietman TM, Martin DL. Biannual versus annual mass azithromycin distribution and malaria seroepidemiology among preschool children in Niger: a sub-study of a cluster randomized trial. Malar J. 2019 Dec 3;18(1):389. doi: 10.1186/s12936-019-3033-2.

Reference Type DERIVED
PMID: 31796025 (View on PubMed)

Kim JS, Oldenburg CE, Cooley G, Amza A, Kadri B, Nassirou B, Cotter SY, Stoller NE, West SK, Bailey RL, Keenan JD, Gaynor BD, Porco TC, Lietman TM, Martin DL. Community-level chlamydial serology for assessing trachoma elimination in trachoma-endemic Niger. PLoS Negl Trop Dis. 2019 Jan 28;13(1):e0007127. doi: 10.1371/journal.pntd.0007127. eCollection 2019 Jan.

Reference Type DERIVED
PMID: 30689671 (View on PubMed)

Keenan JD, Chin SA, Amza A, Kadri B, Nassirou B, Cevallos V, Cotter SY, Zhou Z, West SK, Bailey RL, Porco TC, Lietman TM; Rapid Elimination of Trachoma (PRET) Study Group. The Effect of Antibiotic Selection Pressure on the Nasopharyngeal Macrolide Resistome: A Cluster-randomized Trial. Clin Infect Dis. 2018 Nov 13;67(11):1736-1742. doi: 10.1093/cid/ciy339.

Reference Type DERIVED
PMID: 29897440 (View on PubMed)

O'Brien KS, Cotter SY, Amza A, Kadri B, Nassirou B, Stoller NE, Zhou Z, West SK, Bailey RL, Keenan JD, Porco TC, Lietman TM. Childhood Mortality After Mass Distribution of Azithromycin: A Secondary Analysis of the PRET Cluster-randomized Trial in Niger. Pediatr Infect Dis J. 2018 Nov;37(11):1082-1086. doi: 10.1097/INF.0000000000001992.

Reference Type DERIVED
PMID: 29561511 (View on PubMed)

Oldenburg CE, Amza A, Kadri B, Nassirou B, Cotter SY, Stoller NE, West SK, Bailey RL, Porco TC, Gaynor BD, Keenan JD, Lietman TM. Comparison of Mass Azithromycin Coverage Targets of Children in Niger: A Cluster-Randomized Trachoma Trial. Am J Trop Med Hyg. 2018 Feb;98(2):389-395. doi: 10.4269/ajtmh.17-0501. Epub 2017 Dec 14.

Reference Type DERIVED
PMID: 29260659 (View on PubMed)

Oldenburg CE, Amza A, Kadri B, Nassirou B, Cotter SY, Stoller NE, West SK, Bailey RL, Porco TC, Keenan JD, Lietman TM, Gaynor BD. Annual Versus Biannual Mass Azithromycin Distribution and Malaria Parasitemia During the Peak Transmission Season Among Children in Niger. Pediatr Infect Dis J. 2018 Jun;37(6):506-510. doi: 10.1097/INF.0000000000001813.

Reference Type DERIVED
PMID: 29088030 (View on PubMed)

Amza A, Kadri B, Nassirou B, Cotter SY, Stoller NE, West SK, Bailey RL, Porco TC, Gaynor BD, Keenan JD, Lietman TM, Oldenburg CE. Effectiveness of expanding annual mass azithromycin distribution treatment coverage for trachoma in Niger: a cluster randomised trial. Br J Ophthalmol. 2018 May;102(5):680-686. doi: 10.1136/bjophthalmol-2017-310916. Epub 2017 Sep 11.

Reference Type DERIVED
PMID: 28893761 (View on PubMed)

Bojang E, Jafali J, Perreten V, Hart J, Harding-Esch EM, Sillah A, Mabey DC, Holland MJ, Bailey RL, Roca A, Burr SE. Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control. BMC Microbiol. 2017 Mar 28;17(1):75. doi: 10.1186/s12866-017-0982-x.

Reference Type DERIVED
PMID: 28351345 (View on PubMed)

Amza A, Kadri B, Nassirou B, Cotter SY, Stoller NE, Zhou Z, Bailey RL, Mabey DC, Porco TC, Keenan JD, Gaynor BD, West SK, Lietman TM. A Cluster-Randomized Trial to Assess the Efficacy of Targeting Trachoma Treatment to Children. Clin Infect Dis. 2017 Mar 15;64(6):743-750. doi: 10.1093/cid/ciw810.

Reference Type DERIVED
PMID: 27956455 (View on PubMed)

Liu F, Porco TC, Amza A, Kadri B, Nassirou B, West SK, Bailey RL, Keenan JD, Lietman TM. Short-term forecasting of the prevalence of clinical trachoma: utility of including delayed recovery and tests for infection. Parasit Vectors. 2015 Oct 22;8:535. doi: 10.1186/s13071-015-1115-8.

Reference Type DERIVED
PMID: 26489933 (View on PubMed)

Liu F, Porco TC, Amza A, Kadri B, Nassirou B, West SK, Bailey RL, Keenan JD, Solomon AW, Emerson PM, Gambhir M, Lietman TM. Short-term Forecasting of the Prevalence of Trachoma: Expert Opinion, Statistical Regression, versus Transmission Models. PLoS Negl Trop Dis. 2015 Aug 24;9(8):e0004000. doi: 10.1371/journal.pntd.0004000. eCollection 2015 Aug.

Reference Type DERIVED
PMID: 26302380 (View on PubMed)

Burr SE, Hart J, Edwards T, Harding-Esch EM, Holland MJ, Mabey DC, Sillah A, Bailey RL. Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control. BMC Public Health. 2014 Nov 18;14:1176. doi: 10.1186/1471-2458-14-1176.

Reference Type DERIVED
PMID: 25407464 (View on PubMed)

Gaynor BD, Amza A, Gebresailassie S, Kadri B, Nassirou B, Stoller NE, Yu SN, Cuddapah PA, Keenan JD, Lietman TM. Importance of including borderline cases in trachoma grader certification. Am J Trop Med Hyg. 2014 Sep;91(3):577-9. doi: 10.4269/ajtmh.13-0658. Epub 2014 Jul 7.

Reference Type DERIVED
PMID: 25002297 (View on PubMed)

Hart JD, Edwards T, Burr SE, Harding-Esch EM, Takaoka K, Holland MJ, Sillah A, Mabey DC, Bailey RL. Effect of azithromycin mass drug administration for trachoma on spleen rates in Gambian children. Trop Med Int Health. 2014 Feb;19(2):207-11. doi: 10.1111/tmi.12234. Epub 2014 Jan 17.

Reference Type DERIVED
PMID: 24433194 (View on PubMed)

Harding-Esch EM, Sillah A, Edwards T, Burr SE, Hart JD, Joof H, Laye M, Makalo P, Manjang A, Molina S, Sarr-Sissoho I, Quinn TC, Lietman T, Holland MJ, Mabey D, West SK, Bailey R; Partnership for Rapid Elimination of Trachoma (PRET) study group. Mass treatment with azithromycin for trachoma: when is one round enough? Results from the PRET Trial in the Gambia. PLoS Negl Trop Dis. 2013 Jun 13;7(6):e2115. doi: 10.1371/journal.pntd.0002115. Print 2013.

Reference Type DERIVED
PMID: 23785525 (View on PubMed)

Yohannan J, Munoz B, Mkocha H, Gaydos CA, Bailey R, Lietman TA, Quinn T, West SK. Can we stop mass drug administration prior to 3 annual rounds in communities with low prevalence of trachoma?: PRET Ziada trial results. JAMA Ophthalmol. 2013 Apr;131(4):431-6. doi: 10.1001/jamaophthalmol.2013.2356.

Reference Type DERIVED
PMID: 23392481 (View on PubMed)

Amza A, Kadri B, Nassirou B, Yu SN, Stoller NE, Bhosai SJ, Zhou Z, McCulloch CE, West SK, Bailey RL, Keenan JD, Lietman TM, Gaynor BD. The easiest children to reach are most likely to be infected with ocular Chlamydia trachomatis in trachoma endemic areas of Niger. PLoS Negl Trop Dis. 2013;7(1):e1983. doi: 10.1371/journal.pntd.0001983. Epub 2013 Jan 10.

Reference Type DERIVED
PMID: 23326612 (View on PubMed)

Amza A, Kadri B, Nassirou B, Stoller NE, Yu SN, Zhou Z, Chin S, West SK, Bailey RL, Mabey DC, Keenan JD, Porco TC, Lietman TM, Gaynor BD; PRET Partnership. Community risk factors for ocular Chlamydia infection in Niger: pre-treatment results from a cluster-randomized trachoma trial. PLoS Negl Trop Dis. 2012;6(4):e1586. doi: 10.1371/journal.pntd.0001586. Epub 2012 Apr 24.

Reference Type DERIVED
PMID: 22545165 (View on PubMed)

Harding-Esch EM, Edwards T, Mkocha H, Munoz B, Holland MJ, Burr SE, Sillah A, Gaydos CA, Stare D, Mabey DC, Bailey RL, West SK; PRET Partnership. Trachoma prevalence and associated risk factors in the gambia and Tanzania: baseline results of a cluster randomised controlled trial. PLoS Negl Trop Dis. 2010 Nov 2;4(11):e861. doi: 10.1371/journal.pntd.0000861.

Reference Type DERIVED
PMID: 21072224 (View on PubMed)

Other Identifiers

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NA_00018439

Identifier Type: -

Identifier Source: org_study_id

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