Uncomplicated Plasmodium Falciparum MalariaNCT01849640
Antimalarial Drug Resistance With Assessment of Transmission Blocking Activity
A study testing DHA-piperaquine and Primaquine in people with Uncomplicated Plasmodium Falciparum Malaria, run by David Saunders at 1 site in Cambodia.
Trial summary
This is a two-arm, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a three-day course of Dihydroartemisinin-Piperaquine (DP) with or without single-dose primaquine in patients with uncomplicated Plasmodium falciparum malaria. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Uncomplicated Plasmodium Falciparum Malaria
- What is being tested?
- DHA-piperaquine and Primaquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteCambodia
- Study dates
- Dec 2012to Jun 2016
- Phase
- Interventional
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Volunteer with uncomplicated P. falciparum malaria (volunteers with mixed P. falciparum and P. vivax infections may be enrolled), 18-65 years of age
- Baseline asexual parasite density between 1,000-200,000 parasites/uL
- Able to provide informed consent
- Available and agree to follow-up for anticipated study duration including 3 day treatment course at the MTF and weekly follow-up for the 42-day period
- Authorized by local commander to participate if active duty military
Who cannot join
- Allergic reaction or contraindication to DHA, piperaquine or primaquine
- Significant acute comorbidity requiring urgent medical intervention
- Signs/symptoms and parasitological confirmation of severe malaria
- Use of any anti-malarial within the past 14 days.
- Class I or II G6PD deficiency (defined as severe) as determined at screening
- Pregnant or lactating female, or female of childbearing age, up to 50 years of age, who does not agree to use an acceptable form of contraception during the study
Show all 9Show fewer
- Clinically significant abnormal EKG, including a QTcF interval > 500 ms at enrollment.
- Known or suspected concomitant use of QTc prolonging medications.
- Judged by the investigator to be otherwise unsuitable for study participation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Active Surveillance for P. Falciparum Drug Resistance With Assessment of Transmission Blocking Activity of Single Dose Primaquine in Cambodia
This is a two-arm, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a three-day course of Dihydroartemisinin-Piperaquine (DP) with or without single-dose primaquine in patients with uncomplicated Plasmodium falciparum malaria. On the last day of DP therapy, volunteers will be randomized to receive either a single 45 mg dose of primaquine (PQ) or DP treatment only (no primaquine).
Read the detailed description
Volunteers with uncomplicated malaria in Cambodia will be enrolled to current standard of care therapy with DHA-piperaquine to monitor therapeutic efficacy and measure resistance. The cardiac safety of piperaquine will be monitored with electrocardiograms during the treatment period. Resistance to DP and DP-PQ will be assessed by a combination of clinical, pharmacologic, and parasitologic parameters including genomic signatures of selection during careful weekly follow-up visits for 42 days. Volunteers will be randomized on day 3 to either a single 45mg dose of primaquine or no sexual stage therapy to evaluate effects of primaquine on the sexual stages of malaria (gametocytes) and potential transmissibility of infection to Anopheles mosquitoes as compared to those not treated with primaquine.
- Being tested
- DHA-piperaquine and Primaquine
- Keywords
- Malaria, Drug resistance, DHA-piperaquine, Cambodia, Transmission Blocking
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DHA-piperaquine and PrimaquineDrug
Subject will be enrolled in open label fashion to a 3-day treatment course of DHA-piperaquine (DP) by directly observed therapy (DOT, all patients will receive a total of 9 tablets containing 40mg DHA and 320mg of piperaquine in divided doses at 0, 24 and 48 hours (3 tablets once per day) for the 3 day course. At completion of DP treatment volunteers will be randomized in an open label fashion to receive a single 45 mg dose of primaquine or no therapy.
| Study group | Role | What they receive |
|---|---|---|
| DHA-piperaquine with Primaquine | Active comparator | 3-day treatment course of DHA-piperaquine with 45mg single dose primaquine Receives: Drug: DHA-piperaquine and Primaquine |
| DHA-piperaquine without Primaquine | Active comparator | 3-day treatment course of DHA-piperaquine Receives: Drug: DHA-piperaquine and Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical efficacy of DP
Efficacy rates at 42 days (with 95% confidence intervals) for DP with and without single dose primaquine for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.
Measured: 3 years
Secondary outcomes (1)
Efficacy of Primaquine to treat sexual stage gametocyte infection and prevent transmission of P. falciparum gametocytes to mosquitoes.
To detect efficacy of a onetime dose of primaquine after completion of therapy for blood stage infection on gametocytemia that may persist after DP treatment by using comparative rates of sexual stage infections between patients dosed with and without primaquine based on a composite endpoint of light microscopy and PCR detection and staging of gamteocytes with mosquito membrane feeding assay to detect oocysts in sterile lab-reared mosquitoes.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2013 (estimated)
- Study startDec 2012
- Primary completionDec 2014
- Study completionJun 2016 (estimated)
Why it stopped: Poor efficacy of DHA-piperaquine due to likely drug resistance.
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 Uncomplicated Plasmodium Falciparum MalariaStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Saunders
- Sponsor type
- Other government
- Collaborators
- National Centre for Parasitology, Entomology and Malaria Control, Cambodia, Royal Cambodian Armed Forces, US Department of Defense Armed Forces Health Surveillance Center
- Responsible party
- Sponsor-investigator, David Saunders, Armed Forces Research Institute of Medical Sciences, Thailand
- Investigators
- David Saunders, MD, MPH, Principal investigator, Dept. of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (AFRIMS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849640
- Sponsor's protocol ID
- WRAIR#1877
- Other IDs
- HRPO Log Number A-17145
- Status last verified
- Jul 2015
- First submitted
- 27 Feb 2013
- Last updated
- 15 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Saunders DL, Vanachayangkul P, Lon C; U.S. Army Military Malaria Research Program; National Center for Parasitology, Entomology, and Malaria Control (CNM); Royal Cambodian Armed Forces. Dihydroartemisinin-piperaquine failure in Cambodia. N Engl J Med. 2014 Jul 31;371(5):484-5. doi: 10.1056/NEJMc1403007. No abstract available.
PubMed 25075853Spring 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 25877962Vanachayangkul P, Lon C, Spring M, Sok S, Ta-Aksorn W, Kodchakorn C, Pann ST, Chann S, Ittiverakul M, Sriwichai S, Buathong N, Kuntawunginn W, So M, Youdaline T, Milner E, Wojnarski M, Lanteri C, Manning J, Prom S, Haigney M, Cantilena L, Saunders D. Piperaquine Population Pharmacokinetics and Cardiac Safety in Cambodia. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02000-16. doi: 10.1128/AAC.02000-16. Print 2017 May.
PubMed 28193647
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Active Surveillance for P. Falciparum Drug Resistance With Assessment of Transmission Blocking Activity of Single Dose Primaquine in Cambodia
- ClinicalTrials.gov ID
- NCT01849640
- Acronym / sponsor ID
- WRAIR#1877
- Keywords
- Malaria, Drug resistance, DHA-piperaquine, Cambodia, Transmission Blocking
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Poor efficacy of DHA-piperaquine due to likely drug resistance.
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- David SaundersOther government
- Collaborators
- National Centre for Parasitology, Entomology and Malaria Control, Cambodia, Royal Cambodian Armed Forces, US Department of Defense Armed Forces Health Surveillance Center
- Study start
- Dec 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jun 2016 (estimated)
- First posted
- 8 May 2013 (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.
This is a two-arm, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a three-day course of Dihydroartemisinin-Piperaquine (DP) with or without single-dose primaquine in patients with uncomplicated Plasmodium falciparum malaria. On the last day of DP therapy, volunteers will be randomized to receive either a single 45 mg dose of primaquine (PQ) or DP treatment only (no primaquine).
Detailed description
Volunteers with uncomplicated malaria in Cambodia will be enrolled to current standard of care therapy with DHA-piperaquine to monitor therapeutic efficacy and measure resistance. The cardiac safety of piperaquine will be monitored with electrocardiograms during the treatment period. Resistance to DP and DP-PQ will be assessed by a combination of clinical, pharmacologic, and parasitologic parameters including genomic signatures of selection during careful weekly follow-up visits for 42 days. Volunteers will be randomized on day 3 to either a single 45mg dose of primaquine or no sexual stage therapy to evaluate effects of primaquine on the sexual stages of malaria (gametocytes) and potential transmissibility of infection to Anopheles mosquitoes as compared to those not treated with primaquine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DHA-piperaquine with Primaquine | Active comparator | Drug: DHA-piperaquine and Primaquine3-day treatment course of DHA-piperaquine with 45mg single dose primaquine |
| DHA-piperaquine without Primaquine | Active comparator | Drug: DHA-piperaquine and Primaquine3-day treatment course of DHA-piperaquine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Volunteer with uncomplicated P. falciparum malaria (volunteers with mixed P. falciparum and P. vivax infections may be enrolled), 18-65 years of age
- Baseline asexual parasite density between 1,000-200,000 parasites/uL
- Able to provide informed consent
- Available and agree to follow-up for anticipated study duration including 3 day treatment course at the MTF and weekly follow-up for the 42-day period
- Authorized by local commander to participate if active duty military
Key exclusion criteria (9 listed)
- Allergic reaction or contraindication to DHA, piperaquine or primaquine
- Significant acute comorbidity requiring urgent medical intervention
- Signs/symptoms and parasitological confirmation of severe malaria
- Use of any anti-malarial within the past 14 days.
- Class I or II G6PD deficiency (defined as severe) as determined at screening
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 |
|---|---|---|
| DHA-piperaquine and PrimaquineSubject will be enrolled in open label fashion to a 3-day treatment course of DHA-piperaquine (DP) by directly observed therapy (DOT, all patients will receive a total of 9 tablets containing 40mg DHA and 320mg of piperaquine in divided doses at 0, 24 and 48 hours (3 tablets once per day) for the 3 day course. At completion of DP treatment volunteers will be randomized in an open label fashion to receive a single 45 mg dose of primaquine or no therapy. | Drug | DHA-piperaquine with Primaquine, DHA-piperaquine without Primaquine |
Primary outcome
Clinical efficacy of DP
Time frame: 3 years
Efficacy rates at 42 days (with 95% confidence intervals) for DP with and without single dose primaquine for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.
1 secondary outcome
Efficacy of Primaquine to treat sexual stage gametocyte infection and prevent transmission of P. falciparum gametocytes to mosquitoes.
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2015.
- Background: PubMed 25075853Saunders DL, Vanachayangkul P, Lon C; U.S. Army Military Malaria Research Program; National Center for Parasitology, Entomology, and Malaria Control (CNM); Royal Cambodian Armed Forces. Dihydroartemisinin-piperaquine failure in Cambodia. N Engl J Med. 2014 Jul 31;371(5):484-5. doi: 10.1056/NEJMc1403007. No abstract available.
- Results publication: 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.
- Derived from this study: PubMed 28193647Vanachayangkul P, Lon C, Spring M, Sok S, Ta-Aksorn W, Kodchakorn C, Pann ST, Chann S, Ittiverakul M, Sriwichai S, Buathong N, Kuntawunginn W, So M, Youdaline T, Milner E, Wojnarski M, Lanteri C, Manning J, Prom S, Haigney M, Cantilena L, Saunders D. Piperaquine Population Pharmacokinetics and Cardiac Safety in Cambodia. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02000-16. doi: 10.1128/AAC.02000-16. Print 2017 May.
- Interim ResultsLink provided by the sponsor.
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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.
David Saunders, MD, MPH principal investigator
Dept. of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (AFRIMS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DHA-piperaquine and Primaquine in people with Uncomplicated Plasmodium Falciparum Malaria, run by David Saunders 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 9 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: paused, as of the sponsor's last update on 15 Jul 2015. 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.
Are results available for this study?
Results are not available in the source record.
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?
Clinical efficacy of DP (time frame: 3 years). 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 NCT01849640, 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 15 Jul 2015.