Trial Outcomes & Findings for Efficacy and Safety of a Multi-dose Regimen of Mebendazole Against Hookworm in Children (NCT NCT03245398)

NCT ID: NCT03245398

Last Updated: 2019-06-17

Results Overview

Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 186 participants
• Primary outcome timeframe: baseline (before treatment) and 18 to 22 days post-treatment
• Results posted on: 2019-06-17

Participant Flow

Participant milestones

Measure	Single 500 mg Dose of Mebendazole In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Overall Study STARTED	93	93
Overall Study COMPLETED	92	93
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Single 500 mg Dose of Mebendazole In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Overall Study Travelled to another island	1	0

Baseline Characteristics

Efficacy and Safety of a Multi-dose Regimen of Mebendazole Against Hookworm in Children

Baseline characteristics by cohort

Measure	Single 500 mg Dose of Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Total n=186 Participants Total of all reporting groups
Age, Continuous	10.1 years STANDARD_DEVIATION 1.6 • n=5 Participants	10.1 years STANDARD_DEVIATION 1.6 • n=7 Participants	10.1 years STANDARD_DEVIATION 1.6 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	46 Participants n=7 Participants	85 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	47 Participants n=7 Participants	101 Participants n=5 Participants
Race/Ethnicity, Customized Black	93 Participants n=5 Participants	93 Participants n=7 Participants	186 Participants n=5 Participants
Region of Enrollment Tanzania	93 participants n=5 Participants	93 participants n=7 Participants	186 participants n=5 Participants
Mean weight (kg)	26.7 kg STANDARD_DEVIATION 5.3 • n=5 Participants	26.2 kg STANDARD_DEVIATION 5.1 • n=7 Participants	26.4 kg STANDARD_DEVIATION 5.2 • n=5 Participants
Mean height (cm)	132.0 cm STANDARD_DEVIATION 10.2 • n=5 Participants	131.8 cm STANDARD_DEVIATION 9.6 • n=7 Participants	131.9 cm STANDARD_DEVIATION 9.9 • n=5 Participants
Infected with hookworm	93 Participants n=5 Participants	93 Participants n=7 Participants	186 Participants n=5 Participants
Median EPG hookworm	222 Eggs per gram (EPG) n=5 Participants	222 Eggs per gram (EPG) n=7 Participants	222 Eggs per gram (EPG) n=5 Participants
EPG hookworm (geometric mean)	219 EPG n=5 Participants	234 EPG n=7 Participants	226 EPG n=5 Participants
Light hookworm infection (1-1999 EPG)	89 Participants n=5 Participants	90 Participants n=7 Participants	179 Participants n=5 Participants
Moderate hookworm infection (2000-3999 EPG)	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Heavy hookworm infection (≥4000 EPG)	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Infected with T. trichiura	88 Participants n=5 Participants	91 Participants n=7 Participants	179 Participants n=5 Participants
EPG T. trichiura (geometric mean)	661.8 EPG n=5 Participants	725.7 EPG n=7 Participants	693 EPG n=5 Participants
Light T. trichiura infection (1-999 EPG)	59 Participants n=5 Participants	56 Participants n=7 Participants	115 Participants n=5 Participants
Moderate T. trichiura infection (1000-9999 EPG)	30 Participants n=5 Participants	35 Participants n=7 Participants	65 Participants n=5 Participants
Heavy T. trichiura infection (≥10,000 EPG)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Infected with A. lumbricoides	47 Participants n=5 Participants	51 Participants n=7 Participants	98 Participants n=5 Participants
EPG A. lumbricoides (geometric mean)	2691.2 EPG n=5 Participants	4095.9 EPG n=7 Participants	3349 EPG n=5 Participants
Light A. lumbricoides infection (1-4999 EPG)	28 Participants n=5 Participants	20 Participants n=7 Participants	48 Participants n=5 Participants
Moderate A. lumbricoides infection (5000-49,999 EPG)	15 Participants n=5 Participants	28 Participants n=7 Participants	43 Participants n=5 Participants
Heavy A. lumbricoides infection (≥50,000 EPG)	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Cure Rate (CR) of Mebendazole Against Hookworm	13 percentage of participants cured Interval 6.9 to 21.7	97.9 percentage of participants cured Interval 92.4 to 99.7

SECONDARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Geometric Mean Egg Reduction Rate (ERR) of the Two Regimens of Mebendazole Against Hookworm	-68.0 percentage change Interval -78.6 to -51.5	-100 percentage change Interval -100.0 to -99.9

SECONDARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
CR of Both Mebendazole Regimens Against Trichuris Trichiura	6.8 percentage of participants cured Interval 4.6 to 17.8	42.9 percentage of participants cured Interval 33.8 to 54.8

SECONDARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Geometric ERR of Both Mebendazole Regimens Against Trichuris Trichiura	-71.7 percentage of change Interval -78.5 to -56.7	-98.1 percentage of change Interval -98.7 to -96.8

SECONDARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Cure Rate (CR) of Both Mebendazole Regimens Against Ascaris Lumbricoides	100 percentage of participants cured Interval 100.0 to 100.0	98 percentage of participants cured Interval 94.2 to 100.0

SECONDARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Geometric ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides.	-100 percentage change Interval -100.0 to -100.0	-100 percentage change Interval -100.0 to -100.0

SECONDARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Arithmetic ERR of the Two Regimens of Mebendazole Against Hookworm	-52.7 percentage change Interval -63.6 to -40.3	-99.8 percentage change Interval -100.0 to -99.3

SECONDARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Arithmetic ERR of Both Mebendazole Regimens Against Trichuris Trichiura	-49.1 percentage change Interval -61.0 to -31.7	-91.6 percentage change Interval -94.6 to -88.4

SECONDARY outcome

Timeframe: baseline (before treatment) and 18 to 22 days post-treatment

Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).

Outcome measures

Measure	Single 500 mg Dose of Mebendazole n=92 Participants In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 Participants In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Arithmetic ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides	-100 percentage change Interval -100.0 to -100.0	-99.1 percentage change Interval -100.0 to -96.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

Two aliquots (about 1 g of stool each) of positive samples will be stored in ethanol and transported to the Swiss Tropical Public Health Institute for subsequent DNA extraction and diagnostic.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

The same two aliquots of stool will be used in this section.. Additionally, a Harada Mori culture will be prepared from one of the stool samples of each child at baseline and at follow-up to extract hatched larvae. Larvae will be stored in ethanol. Both stool and larvae samples will undergo an assessment of drug resistance-associated single-nucleotide polymorphisms.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

Genetic differentiation between Necator americanus and Ancylostoma duodenale using PCRs will allow us to identify which of the species is most prevalent.

Outcome measures

Outcome data not reported

Adverse Events

Single 500 mg Dose of Mebendazole

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Single 500 mg Dose of Mebendazole n=93 participants at risk In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days	Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole n=93 participants at risk In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days
Gastrointestinal disorders Abdominal pain	2.2% 2/93 • Adverse event data collected 3h after the first treatment time point	8.6% 8/93 • Adverse event data collected 3h after the first treatment time point

Additional Information

Dr Jennifer Keiser

Swiss Tropical and Public Health Institute

Phone: +41 61 284 8218

Email: jennifer.keiser@swisstph.ch

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place