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Efficacy and Safety of High-dose Ivermectin for Reducing Malaria Transmission: A Dose Finding Study (IVERMAL)

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ClinicalTrials.gov Identifier: NCT02511353
Recruitment Status : Completed
First Posted : July 30, 2015
Last Update Posted : August 23, 2018
Sponsor:
Collaborators:
Kenya Medical Research Institute
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
Liverpool School of Tropical Medicine

Study Description
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Brief Summary:
In western Kenya the prevalence of malaria in <5 year olds has fallen from 70% in 1997 to 40% in 2008, where it has now stagnated. Innovative approaches are needed to continue towards elimination. Ivermectin is a broad spectrum antiparasitic endectocide widely used for the control of onchocerciasis and lymphatic filariasis at a dose of 150-200 mcg/kg. Ivermectin at this dose has a potent, but short-lived effect for 6-11 days on mosquito survival, egg-laying, and parasite sporogony. Higher doses are needed to prolong its mosquitocidal effects. Previous studies have shown ivermectin is very well tolerated and safe even up to 2,000 mcg/kg. This dose finding study will evaluate the transmission blocking effect of high-dose ivermectin to define the optimal dose for future use of ivermectin in combination with artemisinin-based combination therapy (ACT) for mass drug administration (MDA). It explores a research question of global relevance. A prolonged transmission blocking effect of ivermectin could have substantial consequences for malaria control in the next decades. The results are expected to inform national malaria control programs in malaria endemic countries, to inform WHO guidelines, and to contribute to the regulatory process.

Condition or disease Intervention/treatment Phase
Malaria Drug: ivermectin Drug: placebo Drug: dihydroartemisinin-piperaquine Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 141 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of High-dose Ivermectin for Reducing Malaria Transmission: A Dose Finding Study (IVERMAL)
Actual Study Start Date : July 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria
Drug Information available for: Ivermectin

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: placebo
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: placebo 600 mcg/kg/day.
 Drug: placebo
Placebo for ivermectin.

Drug: dihydroartemisinin-piperaquine
Experimental: ivermectin 300 mcg/kg
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 300 mcg/kg/day and placebo 300 mcg/kg/day.
 Drug: ivermectin
Drug: placebo
Placebo for ivermectin.

Drug: dihydroartemisinin-piperaquine
Experimental: ivermectin 600 mcg/kg
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 600 mcg/kg/day.
 Drug: ivermectin
Drug: dihydroartemisinin-piperaquine


Outcome Measures
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Primary Outcome Measures :
  1. Mosquito survival [ Time Frame: Survival of mosquitoes at 14 days after feeding on blood taking from study participants who started the 3-day ivermectin and DP regimen 7 days earlier. ]

Secondary Outcome Measures :
  1. Mosquito survival [ Time Frame: Survival of mosquitoes at each day up to day 21 or 28 after each feeding experiments performed at 0, 2 day+4h, 10, 14, 21, 28 days after start of treatment. ]
  2. Number of patients with malaria clinical and parasitological treatment response [ Time Frame: Up to day 28. ]
  3. Area under the plasma concentration versus time curve (AUC) of ivermectin [ Time Frame: Up to day 28. ]
  4. Area under the plasma concentration versus time curve (AUC) of piperaquine [ Time Frame: Up to day 28. ]
    Dihydroartemisinin-piperaquine is a combination drug. As dihydroartemisinin has a very short elimination time, only the AUC for the longer acting piperaquine component will be determined.

  5. Peak plasma Concentration (Cmax) of ivermectin [ Time Frame: Up to day 28. ]
  6. Peak plasma Concentration (Cmax) of piperaquine [ Time Frame: Up to day 28. ]
    Dihydroartemisinin-piperaquine is a combination drug. As dihydroartemisinin has a very short elimination time, only the Cmax for the longer acting piperaquine component will be determined.

  7. Tolerability as assessed by adverse events reported in a general toxicity questionnaire [ Time Frame: Up to day 28. ]
  8. CNS adverse events [ Time Frame: Up to day 28. ]
  9. Serious adverse events [ Time Frame: Up to day 28. ]
  10. Haemoglobin concentrations [ Time Frame: Up to day 28. ]
  11. QTc interval [ Time Frame: At 52 hours. ]
  12. Mydriasis quantitated by pupillometry [ Time Frame: Up to day 28. ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Symptomatic, uncomplicated Plasmodium falciparum infection
  • Positive malaria microscopy or malaria RDT (pLDH)
  • Age: 18-50 years
  • Provide written informed consent
  • Agree to be able to travel to clinic on days: 1, 2, 7, 10, 14, 21, and 28

Exclusion Criteria:

  • Signs or symptoms of severe malaria
  • Unable to provide written informed consent
  • For women: pregnancy or lactation
  • Hypersensitivity to ivermectin or DP
  • QTc >460 ms on ECG
  • Body Mass Index (BMI) below 16 or above 32 kg/m2
  • Haemoglobin concentration below 9 g/dL
  • Taken ivermectin in the last month
  • Taken dihydroartemisinin-piperaquine in the last 12 weeks
  • Loa loa as assessed by travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan
  • History and/or symptoms indicating chronic illness
  • Current use of tuberculosis or anti-retroviral medication
  • Previously enrolled in the same study
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02511353


Locations
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Kenya
Jaramogi Oginga Odinga Teaching and Referral Hospital
Kisumu, Kenya, 40100
Sponsors and Collaborators
Liverpool School of Tropical Medicine
Kenya Medical Research Institute
Centers for Disease Control and Prevention
Investigators
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Principal Investigator: Menno R. Smit, MD, MPH Liverpool School of Tropical Medicine
Principal Investigator: Feiko ter Kuile, Prof. Liverpool School of Tropical Medicine
More Information
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Publications of Results:

Other Publications:

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Responsible Party: Liverpool School of Tropical Medicine
ClinicalTrials.gov Identifier: NCT02511353     History of Changes
Other Study ID Numbers: 14.002
2775 ( Other Identifier: Kenya Medical Research Institute )
6720 ( Other Identifier: Centers for Disease Control and Prevention )
First Posted: July 30, 2015    Key Record Dates
Last Update Posted: August 23, 2018
Last Verified: August 2018

Keywords provided by Liverpool School of Tropical Medicine:
malaria
plasmodium
dihydroartemisinin-piperaquine
ivermectin

Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Piperaquine
Dihydroartemisinin
Artemisinins
 Ivermectin
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents