Acute Falciparum MalariaPhase 1NCT02612545
Efficacy, Safety, and Tolerability of Dihydroartemisinin-piperaquine + Mefloquine Compared to Dihydroartemisinin-piperaquine or Artesunate-mefloquine in Patients With Uncomplicated Falciparum Malaria in Cambodia
A Phase 1 study testing Dihydroartemisinin-piperaquine (DHA-PPQ) and Mefloquine (MQ) in people with Acute Falciparum Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Cambodia.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 65 years
- Conditions the study is for
- Acute Falciparum Malaria
- What is being tested?
- Dihydroartemisinin-piperaquine (DHA-PPQ) and Mefloquine (MQ)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 216 participants
- Where
- 1 siteCambodia
- Study dates
- 20 Nov 2015to 8 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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%
Show all 21Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Cambodia1 site
National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H
Phnom Penh
About this study
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
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.
Read more
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.
Read the detailed description
Dihydroartemisinin-piperaquine (DHA-PPQ) Cambodia s frontline artemisinin (ART) combination therapy (ACT) for Plasmodium falciparum malaria is failing to cure nearly half of patients in its western provinces. These treatment failures are caused by parasite strains that are resistant to both ART and PPQ, yet sensitive to mefloquine (MQ) in vitro and in vivo. These findings, and previous studies showing that PPQ treats MQ-resistant infections in patients, led us to hypothesize that parasites have not developed cross-resistance to both PPQ and MQ. Given that DHA-PPQ and AS+MQ have both failed rapidly to resistance when used alone, we propose to treat patients with triple ACT (TACT) containing DHA-PPQ + MQ. We believe that this TACT will more effectively cure patients than either ACT alone, and will continue to achieve acceptably high cure rates and help to eliminate malaria in Cambodia until new drugs are developed and deployed. This protocol thus aims to measure the efficacy, safety, and tolerability of DHA-PPQ + MQ versus DHA-PPQ or AS-MQ alone in a multi-site, open-label, randomized clinical trial. In each of three Cambodian provinces (Pursat, Preah Vihear, and Ratanakiri) where DHA-PPQ is failing, we will recruit subjects aged 2 to 65 years with uncomplicated falciparum malaria (randomized 1:1), In Pursat and Preah Vihear we will treat them with either DHA-PPQ + MQ or AS-MQ alone and in Ratanakiri we will treat them with either DHA-PPQ + MQ or DHA-PPQ alone for three days, and follow them for 42 days to assess for recrudescent parasitemia an indicator of treatment failure. The main safety concern of this study is that DHA-PPQ + MQ may cause electrocardiographic (ECG) changes that could predispose a patient to develop clinically significant arrhythmias. This is because PPQ is known to cause prolongation of the ECG corrected QT (QTc) interval, and MQ may further increase PPQ levels (and thus the risk of further QTc prolongation) through pharmacokinetic interactions involving CYP3A4, a liver enzyme that metabolizes both drugs. To monitor for such an event, we will obtain ECG recordings before and after each drug dose. The safety and tolerability of TACT versus ACT will also be assessed through periodic tests of hematopoietic, hepatic, and renal function, and frequent symptom questionnaires. We will also administer a single low dose of primaquine, which kills P. falciparum gametocytes, on Day 2 to interrupt the transmission of parasites to mosquitoes and promote the elimination of malaria in Cambodia. During hospitalization and followup, we will obtain a series of research blood samples to estimate the prevalence of genetic markers for ART, PPQ, and MQ resistance; to develop a genotyping platform for rapidly surveying known drug resistance-associated mutations; investigate the genomic and transcriptomic basis of drug-resistance mechanisms; confirm the elimination of parasites and gametocytes from the bloodstream using sensitive molecular methods; measure the ex-vivo susceptibility of parasites to antimalarial drugs, and cryopreserve parasites for future studies to elucidate the molecular mechanisms of drug resistance.
- Conditions
- Acute Falciparum Malaria
- Being tested
- Dihydroartemisinin-piperaquine (DHA-PPQ), Mefloquine (MQ)
- Keywords
- Plasmodium Falciparum, Artemisinin Combination Therapy, Triple Artemisinin Combination Therapy, Piperaquine, Mefloquine
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dihydroartemisinin-piperaquine (DHA-PPQ)Drug
Co-formulated anti-malarial drug used as standard of care treatment for uncomplicated malaria in Cambodia
Mefloquine (MQ)Drug
ACT partner drug
| Study group | Role | What they receive |
|---|---|---|
| ACT | Active comparator | Patients randomized to ACT will receive DHA-PPQ only Receives: Drug: Dihydroartemisinin-piperaquine (DHA-PPQ) |
| TACT | Experimental | Patients randomized to TACT will receive DHA-PPQ plus MQ Receives: Drug: Dihydroartemisinin-piperaquine (DHA-PPQ); Drug: Mefloquine (MQ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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...
Measured: Day 42 post enrollment
Secondary outcomes (3)
Compare parasite and fever clearance rates/times following TACT versus ACT
Measured: Days 0-6 post enrollment
Compare the safety and tolerability of TACT versus ACT
Measured: Day 0-6 post enrollment
Compare ECG QTc prolongation following TACT versus ACT
Measured: Days 0-2 post enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2015 (estimated)
- Study start20 Nov 2015
- Primary completion12 Oct 2018
- Study completion8 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Falciparum MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 216 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Thomas E Wellems, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02612545
- Sponsor's protocol ID
- 999916023
- Other IDs
- 16-I-N023
- Status last verified
- 8 Oct 2019
- First submitted
- 20 Nov 2015
- Last updated
- 10 Oct 2019
- Results posted
- No
- FDA-regulated device
- No
Publications
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.
PubMed 25075834Leang 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.
PubMed 26014949Spring 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.
PubMed 25877962
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02612545
- Acronym / sponsor ID
- 999916023
- Conditions
- Acute Falciparum Malaria
- Keywords
- Plasmodium Falciparum, Artemisinin Combination Therapy, Triple Artemisinin Combination Therapy, Piperaquine, Mefloquine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 216 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 20 Nov 2015
- Primary completion
- 12 Oct 2018 (actual)
- Study completion
- 8 Oct 2019 (actual)
- First posted
- 24 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Dihydroartemisinin-piperaquine (DHA-PPQ) Cambodia s frontline artemisinin (ART) combination therapy (ACT) for Plasmodium falciparum malaria is failing to cure nearly half of patients in its western provinces. These treatment failures are caused by parasite strains that are resistant to both ART and PPQ, yet sensitive to mefloquine (MQ) in vitro and in vivo. These findings, and previous studies showing that PPQ treats MQ-resistant infections in patients, led us to hypothesize that parasites have not developed cross-resistance to both PPQ and MQ. Given that DHA-PPQ and AS+MQ have both failed rapidly to resistance when used alone, we propose to treat patients with triple ACT (TACT) containing DHA-PPQ + MQ. We believe that this TACT will more effectively cure patients than either ACT alone, and will continue to achieve acceptably high cure rates and help to eliminate malaria in Cambodia until new drugs are developed and deployed. This protocol thus aims to measure the efficacy, safety, and tolerability of DHA-PPQ + MQ versus DHA-PPQ or AS-MQ alone in a multi-site, open-label, randomized clinical trial. In each of three Cambodian provinces (Pursat, Preah Vihear, and Ratanakiri) where DHA-PPQ is failing, we will recruit subjects aged 2 to 65 years with uncomplicated falciparum malaria (randomized 1:1), In Pursat and Preah Vihear we will treat them with either DHA-PPQ + MQ or AS-MQ alone and in Ratanakiri we will treat them with either DHA-PPQ + MQ or DHA-PPQ alone for three days, and follow them for 42 days to assess for recrudescent parasitemia an indicator of treatment failure. The main safety concern of this study is that DHA-PPQ + MQ may cause electrocardiographic (ECG) changes that could predispose a patient to develop clinically significant arrhythmias. This is because PPQ is known to cause prolongation of the ECG corrected QT (QTc) interval, and MQ may further increase PPQ levels (and thus the risk of further QTc prolongation) through pharmacokinetic interactions involving CYP3A4, a liver enzyme that metabolizes both drugs. To monitor for such an event, we will obtain ECG recordings before and after each drug dose. The safety and tolerability of TACT versus ACT will also be assessed through periodic tests of hematopoietic, hepatic, and renal function, and frequent symptom questionnaires. We will also administer a single low dose of primaquine, which kills P. falciparum gametocytes, on Day 2 to interrupt the transmission of parasites to mosquitoes and promote the elimination of malaria in Cambodia. During hospitalization and followup, we will obtain a series of research blood samples to estimate the prevalence of genetic markers for ART, PPQ, and MQ resistance; to develop a genotyping platform for rapidly surveying known drug resistance-associated mutations; investigate the genomic and transcriptomic basis of drug-resistance mechanisms; confirm the elimination of parasites and gametocytes from the bloodstream using sensitive molecular methods; measure the ex-vivo susceptibility of parasites to antimalarial drugs, and cryopreserve parasites for future studies to elucidate the molecular mechanisms of drug resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ACT | Active comparator | Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)Patients randomized to ACT will receive DHA-PPQ only |
| TACT | Experimental | Drug: Dihydroartemisinin-piperaquine (DHA-PPQ), Drug: Mefloquine (MQ)Patients randomized to TACT will receive DHA-PPQ plus MQ |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (21 listed)
- 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
- Hematocrit <25%
- Acute illness other than uncomplicated falciparum malaria requiring treatment
- Pregnancy or breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dihydroartemisinin-piperaquine (DHA-PPQ)Co-formulated anti-malarial drug used as standard of care treatment for uncomplicated malaria in Cambodia | Drug | ACT, TACT |
| Mefloquine (MQ)ACT partner drug | Drug | TACT |
Primary outcome
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...
Time frame: Day 42 post enrollment
3 secondary outcomes
Compare parasite and fever clearance rates/times following TACT versus ACT
Time frame: Days 0-6 post enrollment
Compare the safety and tolerability of TACT versus ACT
Time frame: Day 0-6 post enrollment
Compare ECG QTc prolongation following TACT versus ACT
Time frame: Days 0-2 post enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2019.
- Background: PubMed 25075834Ashley 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.
- Background: PubMed 26014949Leang 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.
- Background: PubMed 25877962Spring 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas E Wellems, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dihydroartemisinin-piperaquine (DHA-PPQ) and Mefloquine (MQ) in people with Acute Falciparum Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Cambodia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cambodia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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... (time frame: Day 42 post enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02612545, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2019.