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NCT Number: NCT02511353

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

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.

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Key information

Conditions

Malaria Infections Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Jaramogi Oginga Odinga Teaching and Referral Hospital

Kisumu, 40100, Kenya

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ivermectin

Drug

Placebo

Drug

Placebo for ivermectin.

Dihydroartemisinin-Piperaquine

Drug

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Liverpool School of Tropical Medicine

Other

Collaborators

  • Centers for Disease Control and Prevention
  • Kenya Medical Research Institute

Registry information

Official study title

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

Acronym: IVERMAL

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Jul 30, 2015
Registry last updated
Aug 23, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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