Acute Falciparum Malaria Clinical Trial
Official title:
A Multi-Site, Open-Label, Randomized Trial to Assess the Efficacy, Safety, and Tolerability of Dihydroartemisinin-Piperaquine Plus Mefloquine Compared to Dihydroartemisinin-Piperaquine or Artesunate-Mefloquine in Patients With Uncomplicated Falciparum Malaria in Cambodia
| Verified date | October 8, 2019 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 216 |
| Est. completion date | October 8, 2019 |
| Est. primary completion date | October 12, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years to 65 Years |
| Eligibility |
- INCLUSION: - 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 EXCLUSION: - 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 - History of allergy or known contraindication to ART, PPQ, MQ, or PMQ - Splenectomy - Documented or claimed history of cardiac arrythmias, neuropsychiatric disease - Earlier participation in this trial - Any condition that in the opinion of the investigator would render the patient unable to comply with the protocol (e.g., psychiatric disease) - Any health condition that in the opinion of the investigator would confound data analysis (e.g., patients known to be HIV-infected or to have AIDS) or pose unnecessary exposure risks to the patient (e.g., severe malnutrition) |
| Country | Name | City | State |
|---|---|---|---|
| Cambodia | National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H | Phnom Penh |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) |
Cambodia,
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. Erratum in: N Engl J Med. 2014 Aug 21;371(8):786. — View Citation
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. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Compare parasite and fever clearance rates/times following TACT versus ACT | Days 0-6 post enrollment | ||
| Secondary | Compare the safety and tolerability of TACT versus ACT | Day 0-6 post enrollment | ||
| Secondary | Compare ECG QTc prolongation following TACT versus ACT | Days 0-2 post enrollment |