Efficacy, Safety, and Tolerability of Dihydroartemisinin-piperaquine + Mefloquine Compared to Dihydroartemisinin-piperaquine or Artesunate-mefloquine in Patients With Uncomplicated Falciparum Malaria in Cambodia

NCT02612545 | Completed Phase 1

• 2 other identifiers: 99991602316-I-N023
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Malaria is an illness caused by a parasite that enters people s bodies when a mosquito bites them. It can cause fevers, headaches, body aches, and weakness. If not treated, it can make some people very ill. Malaria can be cured. A mix of 2 drugs that has worked well in the past is not working as well in some parts of Cambodia. Researchers want to see if a mix of 3 drugs works better and is safe. Objectives: To see if a 3-drug mix can be used to treat malaria in areas where a 2-drug mix is less effective. Eligibility: People aged 2 65 years with mild malaria in Pursat, Preah Vihear, and Ratanakiri Provinces in Cambodia. Design: Participants will be screened with medical history, physical exam, urine and blood tests, and an electrocardiogram (ECG). For this, electrodes will be placed on their skin to check their heartbeat. Participants will spend about 5 nights in the hospital. They will have physical exams and will complete symptom questionnaires daily. They will give blood periodically throughout their stay. For this, a thin plastic tube is placed in an arm vein for the first day, and blood draws using a needle are done after that. Participants will get either a 2-drug mix or a 3-drug mix for 3 days. They will have 2 ECGs each day of receiving the drugs. Participants will have follow-up visits once a week over 5 weeks. At these visits, they will have a physical exam and have blood taken. If they have any signs of malaria, they will be re-treated. The study will last up to 42 days.

Conditions

Acute Falciparum Malaria

Keywords

Plasmodium Falciparum; Artemisinin Combination Therapy; Triple Artemisinin Combination Therapy; Piperaquine; Mefloquine

Outcome Measures

Primary Outcomes (1)

• Compare the efficacy of TACT versus ACT, as defined by an adequate clinical and parasitological response (ACPR), defined as: absence of parasitemia on Day 42 (detected by blood smear, not PCR), irrespective of tympanic temperature, in subjects w...

  Day 42 post enrollment

Secondary Outcomes (3)

• Compare parasite and fever clearance rates/times following TACT versus ACT

  Days 0-6 post enrollment

• Compare the safety and tolerability of TACT versus ACT

  Day 0-6 post enrollment

• Compare ECG QTc prolongation following TACT versus ACT

  Days 0-2 post enrollment

Study Arms (2)

ACT

ACTIVE COMPARATOR

Patients randomized to ACT will receive DHA-PPQ only

Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)

TACT

EXPERIMENTAL

Patients randomized to TACT will receive DHA-PPQ plus MQ

Drug: Dihydroartemisinin-piperaquine (DHA-PPQ); Drug: Mefloquine (MQ)

Interventions

Dihydroartemisinin-piperaquine (DHA-PPQ) DRUG

Co-formulated anti-malarial drug used as standard of care treatment for uncomplicated malaria in Cambodia

ACT; TACT

Mefloquine (MQ) DRUG

ACT partner drug

TACT

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 2 to 65 years
• Uncomplicated falciparum malaria, confirmed by the presence of asexual P.falciparum parasites (alone or mixed with other Plasmodium species) on blood film
• Asexual P. falciparum count \<200,000/ L at screening
• Tympanic temperature greater than or equal to 37.5 (Infinite)C or history of fever in the previous 24 hours
• Written informed consent from adults or the parents/guardians of children

You may not qualify if:

• Signs of severe malaria, defined as one or more of the following:
• Glasgow Coma Scale less than or equal to 10/15 in adults; Blantyre Coma Scale less than or equal to 3/5 in children
• Witnessed convulsions
• Severe prostration
• Shock (poor perfusion, cool peripheries as deemed by the study physician)
• Hematocrit \<20%
• Jaundice
• Respiratory distress (labored breathing, nasal flaring, intercostal retraction)
• Anuria for 24 hours or more
• Repetitive vomiting
• Hematocrit \<25%
• Acute illness other than uncomplicated falciparum malaria requiring treatment
• Pregnancy or breastfeeding
• Patients who have received an ART derivative or ACT in the previous 7 days
• Treatment with MQ in the previous 60 days

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H

Phnom Penh, Cambodia

Location

Related Publications (3)

• Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B, Sopha C, Chuor CM, Nguon C, Sovannaroth S, Pukrittayakamee S, Jittamala P, Chotivanich K, Chutasmit K, Suchatsoonthorn C, Runcharoen R, Hien TT, Thuy-Nhien NT, Thanh NV, Phu NH, Htut Y, Han KT, Aye KH, Mokuolu OA, Olaosebikan RR, Folaranmi OO, Mayxay M, Khanthavong M, Hongvanthong B, Newton PN, Onyamboko MA, Fanello CI, Tshefu AK, Mishra N, Valecha N, Phyo AP, Nosten F, Yi P, Tripura R, Borrmann S, Bashraheil M, Peshu J, Faiz MA, Ghose A, Hossain MA, Samad R, Rahman MR, Hasan MM, Islam A, Miotto O, Amato R, MacInnis B, Stalker J, Kwiatkowski DP, Bozdech Z, Jeeyapant A, Cheah PY, Sakulthaew T, Chalk J, Intharabut B, Silamut K, Lee SJ, Vihokhern B, Kunasol C, Imwong M, Tarning J, Taylor WJ, Yeung S, Woodrow CJ, Flegg JA, Das D, Smith J, Venkatesan M, Plowe CV, Stepniewska K, Guerin PJ, Dondorp AM, Day NP, White NJ; Tracking Resistance to Artemisinin Collaboration (TRAC). Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014 Jul 31;371(5):411-23. doi: 10.1056/NEJMoa1314981.

  PMID: 25075834 BACKGROUND

• Leang R, Taylor WR, Bouth DM, Song L, Tarning J, Char MC, Kim S, Witkowski B, Duru V, Domergue A, Khim N, Ringwald P, Menard D. Evidence of Plasmodium falciparum Malaria Multidrug Resistance to Artemisinin and Piperaquine in Western Cambodia: Dihydroartemisinin-Piperaquine Open-Label Multicenter Clinical Assessment. Antimicrob Agents Chemother. 2015 Aug;59(8):4719-26. doi: 10.1128/AAC.00835-15. Epub 2015 May 26.

  PMID: 26014949 BACKGROUND

• Spring MD, Lin JT, Manning JE, Vanachayangkul P, Somethy S, Bun R, Se Y, Chann S, Ittiverakul M, Sia-ngam P, Kuntawunginn W, Arsanok M, Buathong N, Chaorattanakawee S, Gosi P, Ta-aksorn W, Chanarat N, Sundrakes S, Kong N, Heng TK, Nou S, Teja-isavadharm P, Pichyangkul S, Phann ST, Balasubramanian S, Juliano JJ, Meshnick SR, Chour CM, Prom S, Lanteri CA, Lon C, Saunders DL. Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis. 2015 Jun;15(6):683-91. doi: 10.1016/S1473-3099(15)70049-6. Epub 2015 Apr 12.

  PMID: 25877962 BACKGROUND

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Mefloquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Thomas E Wellems, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2015
• First Posted: November 24, 2015
• Study Start: November 20, 2015
• Primary Completion: October 12, 2018
• Study Completion: October 8, 2019
• Last Updated: October 10, 2019

Record last verified: 2019-10-08

Locations

CA (1)