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Study Title and Description

Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial.



Key Questions Addressed
1 What is the effect of doxycycline plus ivermectin versus ivermectin alone for treatment of patients with onchocerciasis?
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Primary Publication Information
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TitleData
Title Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial.
Author Turner JD., Tendongfor N., Esum M., Johnston KL., Langley RS., Ford L., Faragher B., Specht S., Mand S., Hoerauf A., Enyong P., Wanji S., Taylor MJ.
Country Filariasis Research Laboratory, Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Year 2010
Numbers Pubmed ID: 20405054

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Doxycycline plus ivermectin versus ivermectin alone for treatment of patients with onchocerciasis 2016
Arms
Number Title Description Comments
1 Doxycyline + Ivermectin 200 mg/d doxycycline for 6 weeks, followed by a single dose of 0.15 mg/kg ivermectin after 4 months
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2 Ivermectin placebo for 6 weeks, followed by a single dose of 0.15 mg/kg ivermectin after 4 months
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3 Doxycycline 200 mg/d doxycycline for 6 weeks, followed by a single placebo after 4 months
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Design Details
Question... Follow Up Answer Follow-up Answer
Page e660
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Study design parallel-group randomized controlled trial
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Number randomly assigned 150 total participants; 60 in the doxycycline plus ivermectin group, 60 in the ivermectin group, and 30 in the doxycycline group
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Exclusions after randomization none reported
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Losses to follow-up At 12 months: 55 total; 24 in the doxycycline plus ivermectin group, 23 in the ivermectin group, and 8 in the doxycycline group (plus an additional 6 participants with Loa loa); At 21 months: 60 total; 28 in the doxycycline plus ivermectin group, 23 in the ivermectin group, and 9 in the doxycycline group (plus an additional 8 participants with Loa loa)
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Number analyzed At 12 months: 95 total; 36 in the doxycycline plus ivermectin group, 37 in the ivermectin group, and 22 in the doxycycline group (plus an additional 16 participants with Loa loa); At 21 months: 90 total; 32 in the doxycycline plus ivermectin group, 37 in the ivermectin group, and 21 in the doxycycline group (plus an additional 14 participants with Loa loa)
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Unit of analysis individual
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Power calculation at least 30 participants were recruited into each treatment group to allow for up to a 15% drop-out rate over the study period and a power of 80%
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Country Cameroon
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Mean age total not provided; per group: 35 years (range 15 to 50) in the doxycycline plus ivermectin group, 37 years (range 16 to 50) in the ivermectin group, and 35 years (range 15 to 50) in the doxycycline group
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Gender 51 (56.7%) men, 39 (43.3%) women; per group: 20 men, 12 women in the doxycycline plus ivermectin group; 18 men, 19 women in the ivermectin group; and 13 men, 8 women in the doxycycline group
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Inclusion criteria &";adults of both sexes aged 15–60, with a minimum body weight of >/= 40 kg, in good health without any clinical condition requiring chronic medication&";
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Exclusion criteria &";an O. volvulus microfilarial load, 10 mf/mg, L. loa microfilarial load > 8000 mf/mL, hepatic and renal enzymes outside of normal ranges (AST [0–40 IU/l, ALT [0–45 IU/l] and creatinine [3–126 mmol/l]), pregnancy, lactation, intolerance to ivermectin, alcohol or drug abuse or anti-filarial therapy in the last 12 months&";
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Equivalence of baseline characteristics yes
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Intervention 1 200 mg/d doxycycline for 6 weeks, followed by a single dose of 0.15 mg/kg ivermectin after 4 months
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Intervention 2 placebo for 6 weeks, followed by a single dose of 0.15 mg/kg ivermectin after 4 months
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Intervention 3 200 mg/d doxycycline for 6 weeks, followed by a single placebo after 4 months
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Length of follow-up Planned: 21 months; Actual: 21 months
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Primary outcome, as defined in study report Primary and secondary outcomes not differentiated
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Secondary outcomes, as defined in study report Primary and secondary outcomes not differentiated
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Adverse events reported yes
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Intervals at which outcomes assessed 4, 12, and 21 months
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Subgroup analyses the safety of doxycycline treatment before ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia was assessed
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Study period 1 July 2003 to 31 March 2005
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Trial registration ISRCTN 48118452
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Funding sources &";the European Commission (ICA4-2002-10051), the Wellcome Trust (Senior Fellowship award to MJT) and the Bill & Melinda Gates Foundation (A-WOL consortium award to the Liverpool School of Tropical Medicine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript&";
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Disclosures of interest &";The authors have declared that no competing interests exist&";
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Main outcomes, as reported in study Number of mf present in skin snip biopsies taken at baseline, 4, 12 and 21 months after start of treatmentClinical monitoring and assessment of adverse reactions during primary drug allocation (doxycycline) or secondary drug allocation (ivermectin) in patients singly infected with O. volvulus or co-infected with L. loa
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Study design issues an additional 22 participants co-infected with Loa loa were not randomly assigned, and all were assigned to the doxycycline plus ivermectin group. Some outcome data were not reported separately for randomized and non-randomized participants
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Random sequence generation (selection bias):Authors' judgement Low risk
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Random sequence generation (selection bias):Support for judgement &";Randomization for onchocerciasis was block stratified based on baseline microfilaridermia. All L. loa co-infected patients were assigned to doxycycline + ivermectin treatment&";
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Allocation concealment (selection bias):Authors' judgement Low risk
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Allocation concealment (selection bias):Support for judgement &";Treatment allocation was assigned by randomized ID code (by JDT and MJT) and the course of treatment sealed in an envelope for allocation by the field team and district field officers&";
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Masking of participants and personnel (performance bias):Authors' judgement Low risk
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Masking of participants and personnel (performance bias):Support for judgement &";All study personnel and participants were blinded to the doxycycline and placebo treatment assignment for the duration of the study&"; &";Placebo tablets for assessment of ivermectin adverse events were not supplied in time for treatment allocation and so unmarked lactose tablets of similar size, shape and colour were used as an alternative. The ivermectin and dummy pills were assigned to individuals in sealed unmarked envelopes before being handed over to district health officers for drug delivery and these together with individuals responsible for the clinical assessment of adverse events were not involved in any subsequent analysis&";
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Masking of outcome assessment (detection bias):Authors' judgement Low risk
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Masking of outcome assessment (detection bias):Support for judgement &";All study personnel and participants were blinded to the doxycycline and placebo treatment assignment for the duration of the study&";
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Incomplete outcome data (attrition bias):Authors' judgement High risk
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Incomplete outcome data (attrition bias):Support for judgement Although &";no significant differences in the drop-out patterns over the follow-up period between the three treatment groups&"; was reported, more than one-third of participants were not included in the final analyses At 12 months, 55 (36.7%) of 150 participants who were randomly assigned were excluded or lost to follow-up, and they were not included in the analysis At 21 months, 60 (40.0%) of 150 participants who were randomly assigned were excluded or lost to follow-up, and they were not included in the analysis
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Selective reporting (reporting bias):Authors' judgement High risk
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Selective reporting (reporting bias):Support for judgement Protocol was not available for assessment of selective outcome reporting; however, some outcome data were not reported separately for randomly assigned and non-randomly assigned participants
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Other bias:Authors' judgement High risk
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Other bias:Support for judgement 22 participants co-infected with L. loa were not randomly assigned; all were assigned to the combination group
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Results & Comparisons

No Results found.
Adverse Events
Arm or Total Title Description Number of events Comments
Doxycyline + Ivermectin Mild or moderate adverse events Mild or moderate adverse events and consisted of itching, fever, headache, body pains, and vertigo, during six weeks of doxycycline treatment 6
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Ivermectin 7
Doxycycline 2
Total 15
Doxycyline + Ivermectin Adverse events Forty-eight hours following ivermectin or placebo allocation, symptoms consistent with adverse reactions. 3
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Ivermectin 7
Doxycycline 3
Total 13