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Trial record 24 of 106 for:    IVERMECTIN

Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study (RIMDAMAL)

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ClinicalTrials.gov Identifier: NCT02509481
Recruitment Status : Completed
First Posted : July 28, 2015
Results First Posted : January 4, 2019
Last Update Posted : January 4, 2019
Sponsor:
Collaborators:
Institut de Recherche en Sciences de la Sante, Burkina Faso
Centre Muraz
Ministère de la Santé du Burkina Faso
Information provided by (Responsible Party):
Colorado State University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Conditions Malaria
Lymphatic Filariasis
Interventions Drug: Ivermectin
Drug: Albendazole
Enrollment 2712
Recruitment Details 2712 participants from 8 villages were recruited to participate and enrolled. Importantly, the intervention (repeated ivermectin MDA) was given to most villagers and the safety outcome was assessed in this whole group. However, the primary outcome was assessed in a cohort of 590 enrolled village children ≤5 years old.
Pre-assignment Details  
Arm/Group Title Single MDA Repeated MDA
Hide Arm/Group Description

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

Period Title: Overall Study
Started 1265 1447
Completed 1265 1447
Not Completed 0 0
Arm/Group Title Single MDA Repeated MDA Total
Hide Arm/Group Description

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

Total of all reporting groups
Overall Number of Baseline Participants 1265 1447 2712
Hide Baseline Analysis Population Description
The total number of enrolled participants were most of population of the eight enrolled villages (2712 participants).
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 1265 participants 1447 participants 2712 participants
14
(7 to 30)
16
(6 to 35)
15
(6 to 34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1265 participants 1447 participants 2712 participants
Female
620
  49.0%
713
  49.3%
1333
  49.2%
Male
645
  51.0%
734
  50.7%
1379
  50.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1265 participants 1447 participants 2712 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1265
 100.0%
1447
 100.0%
2712
 100.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Burkina Faso Number Analyzed 1265 participants 1447 participants 2712 participants
1265
 100.0%
1447
 100.0%
2712
 100.0%
Height <90 cm  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1265 participants 1447 participants 2712 participants
210
  16.6%
267
  18.5%
477
  17.6%
1.Primary Outcome
Title Incidence of Clinical Malaria Episodes
Hide Description Cumulative incidence of malaria episodes in a cohort of village children ≤ 5 years of age (as assessed by active case surveillance in study villages – malaria episode defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum). Incidence is reported as malaria episodes per child over the course of the trial, a higher incidence is a worse outcome.
Time Frame Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Hide Outcome Measure Data
Hide Analysis Population Description
Note that the primary outcome measure comes only from malaria incidence measurements within this child cohort (590 children). It is not a measure of malaria incidence from all enrolled participants from the study villages (2712 participants).
Arm/Group Title Single MDA Repeated MDA
Hide Arm/Group Description:

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

Overall Number of Participants Analyzed 263 327
Mean (95% Confidence Interval)
Unit of Measure: episodes
2.49
(2.28 to 2.73)
2.00
(1.82 to 2.20)
2.Secondary Outcome
Title Adverse Events
Hide Description The number of adverse events. Adverse events data were collected via passive case detection from total population.
Time Frame Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the secondary outcome was a measure of all adverse events, excluding uncomplicated malaria episodes that were reported in the primary outcome, that occurred among the total enrolled population from the study villages (2712 participants).
Arm/Group Title Single MDA Repeated MDA
Hide Arm/Group Description:

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

Overall Number of Participants Analyzed 1265 1447
Measure Type: Number
Unit of Measure: adverse events
24 45
3.Secondary Outcome
Title Entomological Indicator of Parasite Transmission
Hide Description Change in human IgG reactivity (optical density; ∆OD) to an Anopheles salivary gland antigen (peptide gSG6-P1) over the trial period. A score of 0 indicates no change in seroreactivity from from immediately before to immediately after the trial, suggesting consistent mosquito biting throughout the trial. A positive score indicates increasing seroreactivity and thus increasing mosquito biting on participants from immediately before to immediately after the trial. A negative score indicates decreasing seroreactivity and thus decreasing mosquito biting on participants from immediately before to immediately after the trial.
Time Frame Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm
Hide Outcome Measure Data
Hide Analysis Population Description
We sampled finger capillary blood pre-intervention from a subset of enrolled participants located in 8 households at the center of each study village, and then re-sampled their blood immediately after the intervention period. Data were reported only from participants that gave both sets of samples (221 of 2712 participants).
Arm/Group Title Single MDA Repeated MDA
Hide Arm/Group Description:

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

Overall Number of Participants Analyzed 95 126
Mean (95% Confidence Interval)
Unit of Measure: change in IgG ELISA optical density
-0.057
(-0.096 to -0.017)
-0.124
(-0.161 to -0.088)
4.Secondary Outcome
Title Molecular Force of P. Falciparum Infection
Hide Description Examination of new P. falciparum clones acquired from the beginning to the end of the intervention (molecular force of infection; mFOI) per child. Molecular genotyping used capillary blood taken at the time of diagnosis of each positive malaria episode and consisted of nPCR of the msp2 gene. We calculated the multiplicity of infection (MOI) per malaria episode, and then calculated the molecular force of infection (mFOI) associated with malaria episodes per child (over course of the trial)
Time Frame Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm
Hide Outcome Measure Data
Hide Analysis Population Description
Molecular genotyping was performed on blood samples from 132 enrolled cohort children who were selected using a random sequence generator. Genotyping was successful on blood spots corresponding to 153 malaria episodes, which allowed us to calculate the mFOI over the trial from 76 enrolled children from the cohort.
Arm/Group Title Single MDA Repeated MDA
Hide Arm/Group Description:

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

Overall Number of Participants Analyzed 38 38
Median (Inter-Quartile Range)
Unit of Measure: new P. faliciparum infections per child
4
(2 to 7)
3
(2 to 5)
5.Secondary Outcome
Title Number of 6-10 Year Old Participants With Soil Transmitted Helminths (STH)
Hide Description Prevalence of soil transmitted helminth infections in children between 6-10 years old from the beginning to the end of the intervention
Time Frame Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome was only measured in older enrolled children between 6-10 years of age, who were not in our primary outcome cohort, and who were eligible to be treated with ivermectin due to their height >90 cm (232 of 2712 participants).
Arm/Group Title Single MDA Repeated MDA
Hide Arm/Group Description:

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

Overall Number of Participants Analyzed 122 110
Measure Type: Number
Unit of Measure: participants
3 0
6.Secondary Outcome
Title Entomological Inoculation Rate
Hide Description The entomological inoculation rate (EIR per week per person) is the measure of the human biting rate per person per week, multiplied by the sporozoite rate (in biting mosquitoes) per week, an estimated from sampling mosquitoes from 8 households located in the center of each study village. The EIR was calculated for each of the 6 sampling weeks of the treatment phase.
Time Frame 6 sampling periods over 18 weeks, starting in week 2 following the first MDA, and sampling every 3 weeks thereafter until week 17 of the treatment phase.
Hide Outcome Measure Data
Hide Analysis Population Description
The mean EIR was calculated across the 6 sampling periods in the 8 study villages (4 villages in each arm). EIR was calculated from the number of mosquitoes captured in select houses and the number of enrolled participants who lived in each sampled house (324/1265 in single MDA arm, and 271/1447 in repeated MDA arm).
Arm/Group Title Single MDA Repeated MDA
Hide Arm/Group Description:

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

Overall Number of Participants Analyzed 324 271
Mean (Standard Deviation)
Unit of Measure: infectious bites per person per week
0.2069  (0.2376) 0.1972  (0.2084)
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events were measured from the total population of enrolled participants in the eight study villages (n=2712), and most of these participants received the study intervention (ivermectin MDA)
 
Arm/Group Title Single MDA Repeated MDA
Hide Arm/Group Description

Single mass drug administration of ivermectin (150 µg/kg) + albendazole (400 mg) performed after the start of the rainy season as part of public health efforts to eliminate lymphatic filariasis.

Ivermectin

Albendazole

Same as Active Comparator, but then followed by five more mass drug administrations of ivermectin only (150 µg/kg) every three weeks thereafter.

Ivermectin

Albendazole

All-Cause Mortality
Single MDA Repeated MDA
Affected / at Risk (%) Affected / at Risk (%)
Total   5/1265 (0.40%)      15/1447 (1.04%)    
Show Serious Adverse Events Hide Serious Adverse Events
Single MDA Repeated MDA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/1265 (0.79%)      19/1447 (1.31%)    
Cardiac disorders     
untreated decompensated hypertensive heart failure *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
Gastrointestinal disorders     
acute intestinal obstruction *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
abdominal pain, loose stool, vomiting *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
vomiting, hematemesis, bloody stool, cardiovascular shock *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Abdominal bloating, fecal matter obstruction, anuria, refusal to breastfeed *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Hepatobiliary disorders     
liver disease: ascites + bulky edema of the lower limbs. *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
liver cancer, cirrhosis of the liver *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Infections and infestations     
moderate to severe malaria *  7/1265 (0.55%)  7 7/1447 (0.48%)  7
neonatal infection *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
fever, vomiting, anorexia *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
fever, anemia, cachexia *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
severe sepsis *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
fever and chills; suspected typhoid fever *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Injury, poisoning and procedural complications     
snakebite envenomation *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Investigations     
unspecified sudden death in the early morning *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Respiratory, thoracic and mediastinal disorders     
dyspnea *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Infectious pneumopathy *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Single MDA Repeated MDA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/1265 (1.11%)      26/1447 (1.80%)    
Ear and labyrinth disorders     
Perforated bilaterally suppurated otitis *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
acute otitis media *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
suppurative otitis *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Eye disorders     
Bilateral palpebral edema *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
Gastrointestinal disorders     
febrile diarrhea *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Abdominal pain, loose stool, vomiting *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
vomiting *  0/1265 (0.00%)  0 3/1447 (0.21%)  3
General disorders     
Tremor, palpitations, arthralgia *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
 *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Immune system disorders     
pruritis *  1/1265 (0.08%)  1 2/1447 (0.14%)  2
Infections and infestations     
malaria *  2/1265 (0.16%)  2 2/1447 (0.14%)  2
acute malnutrition *  2/1265 (0.16%)  2 5/1447 (0.35%)  5
fever *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
diarrhea *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
stage 3 tooth decay with local tumefaction *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
headache and chills; suspected infectious origin *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
fever and chills; suspected typhoid *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Injury, poisoning and procedural complications     
unspecified injury *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
snakebite envenomation *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
first degree burn over 80% of lower right limb *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
unspecified injury *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
road accident *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Musculoskeletal and connective tissue disorders     
Swelling of the feet, hyperthermia and chills *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Pregnancy, puerperium and perinatal conditions     
Involuntary abortion at two months of pregnancy *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Postpartum pelvic pain *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
Skin and subcutaneous tissue disorders     
intercostal zoster from immune system depression *  1/1265 (0.08%)  1 0/1447 (0.00%)  0
Chronic wound in the left ankle *  0/1265 (0.00%)  0 1/1447 (0.07%)  1
*
Indicates events were collected by non-systematic assessment
We could not provide placebo MDA for the control villages, and the trial was not blinded to the study population or the study team. Adverse event analysis bias may have from the knowledge of the village populace as to what arm they were part of.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Brian D. Foy, Professor
Organization: Colorado State University
Phone: 970-491-3470
EMail: Brian.Foy@colostate.edu
Layout table for additonal information
Responsible Party: Colorado State University
ClinicalTrials.gov Identifier: NCT02509481     History of Changes
Other Study ID Numbers: 5375011
OPP1116536 ( Other Grant/Funding Number: The Bill and Melinda Gates Foundation )
First Submitted: July 23, 2015
First Posted: July 28, 2015
Results First Submitted: July 6, 2018
Results First Posted: January 4, 2019
Last Update Posted: January 4, 2019