Malaria, VivaxPhase 4NCT03337152
Assessing a Risk Model for G6PD Deficiency
A Phase 4 study testing primaquine and chloroquine + primaquine in people with Malaria, Vivax and G6PD Deficiency, run by PATH at 1 site in Thailand.
Trial summary
A clinical study designed to develop and inform an individual risk of hemolysis model based on individual red blood cell G6PD levels. Volunteers who are eligible to treatment with primaquine as per national guidelines and with confirmed normal G6PD levels as per the fluorescent spot test will be exposed to treatment… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Malaria, Vivax, G6PD Deficiency
- What is being tested?
- primaquine and chloroquine + primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteThailand
- Study dates
- 7 May 2018to 21 Oct 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Previous G6PD test at Shoklo Malaria Research Unit (SMRU) clinic with one of following results: 1) G6PD homozygous wildtype females (G6PD genotype normal) 2) G6PD heterozygous females with a normal FST (G6PD genotype abnormal with G6PD activity ≥40% and ≤80% of normal ) 3) G6PD hemizygous wildtype males (G6PD genotype normal)
- Willing to participate and sign informed consent form
- Willing to allow donated samples to be used in future research
- Aged ≥18 years
- Ability (in the investigators' opinion) and willing to comply with all study requirements
Who cannot join
- All participants:
- Malaria or other illness
- Recent history (within 20 days) of anti-malarial treatment
- History of allergy or adverse reaction to chloroquine or primaquine
- Blood transfusion in the past 3 months
- G6PD activity less than 40% normal activity or 3.00 IU/gHb by the quantitative G6PD spectrophotometric assay
Show all 11Show fewer
- Haemoglobin ≤10 g/dL
- Presence of any condition which in the judgment of the investigator would place the subject at undue risk or interfere with the results of the study
- Female participants only:
- Pregnancy at the time of screening
- Breastfeeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Developing a Methodology to Assess 8-aminoquinoline Associated Haemolytic Risk in Females Heterozygous for G6PD in Endemic Populations
A clinical study designed to develop and inform an individual risk of hemolysis model based on individual red blood cell G6PD levels. Volunteers who are eligible to treatment with primaquine as per national guidelines and with confirmed normal G6PD levels as per the fluorescent spot test will be exposed to treatment regimens of either primaquine alone for 14 days or 3 day chloroquine with concomitant primaquine for 14 days. The volunteers will be followed intensively during treatment and for 14 days after treatment for haematologic measures, G6PD quantification, and drug level assays.
Read the detailed description
Open label, randomized trial with 72 total participants assigned to one of two treatment arms. Each arm will have 36 participants comprised of 12 males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD with a normal fluorescent spot test (FST) (G6PD genotype abnormal with G6PD activity ≥40% and ≤80% of normal). Arm 1a will receive primaquine for 14 days, and Arm 1b will receive chloroquine for 3 days and concomitant primaquine for 14 days. All participants will be healthy volunteers without severe G6PD deficiency who will be followed for two weeks after completing their study drug dosing. Pregnant women and those breastfeeding will be excluded. Venous blood samples will be taken at regular intervals for haematologic measures, G6PD quantification, and drug level assays. G6PD levels will be measured both by spectrophotometry to provide whole blood G6PD levels normalized for hemoglobin, as well by flow cytometry to to provide red blood cell G6PD distributions throughout the treatment and post treatment. Changes in the G6PD distributions will be modeled, incorporating other critical haematological indicators collected throughout the study too.
- Conditions
- Malaria, Vivax, G6PD Deficiency
- Being tested
- primaquine, chloroquine + primaquine
- Medical subject headings
- Malaria, Vivax, Glucosephosphate Dehydrogenase Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
primaquineDrug
Participants receive primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed.
chloroquine + primaquineDrug
Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed.
| Study group | Role | What they receive |
|---|---|---|
| 1A: primaquine | Other | Twelve males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD deficiency will be randomized to arm 1A. Participants in arm 1A will receive primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed. Receives: Drug: primaquine |
| 1B: chloroquine + primaquine | Other | Twelve males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD deficiency will be randomized to arm 1B. Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed. Receives: Drug: chloroquine + primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Haemoglobin
The change in haemoglobin from baseline on exposure to primaquine for P.vivax treatment over treatment course to hemoglobin level at day 28.
Measured: 28 days after enrollment
Change in G6PD Concentration
The haemoglobin-related change in G6PD concentration, as determined by spectrometer, over treatment course.
Change is determined from baseline to day 28
Measured: 28 days after enrollment
Secondary outcomes (5)
Significance of CYP2D6
relevance of Dextromethorphan assay results to risk of haemolysis models
Measured: 28 days after enrollment
Association of Drug Levels
Association of chloroquine and primaquine drug levels at the time of sampling for haematological and G6PD profiles.
Measured: Days 1,2,3,5,7,9,11,14,17,21
Serious Adverse Events
frequency of serious adverse events in women heterozygous for G6PD
Measured: 28 days after enrollment
Significance of Reticulocyte Count
relevance of reticulocyte count to risk of haemolysis models
Measured: Days 1,2,3,5,7,9,11,14,17,21
Significance of Urobilinogen Levels
relevance of urobilinogen tests to risk of haemolysis models
Measured: Days 1,2,3,5,7,9,11,14,17,21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study start7 May 2018
- Primary completion21 Aug 2018
- Study completion21 Oct 2018
Why it stopped: study met study halting rules
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malaria, VivaxStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized into one of two arms. 1a will receive primaquine for 14 days, and Arm 1b will receive chloroquine for 3 days and concomitant primaquine for 14 days.
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol Oxford Tropical Medicine Research Unit
- Responsible party
- Sponsor
- Investigators
- François Nosten, MD, PhD, Principal investigator, Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03337152
- Sponsor's protocol ID
- 856370-2
- Status last verified
- May 2019
- First submitted
- 27 Oct 2017
- Last updated
- 12 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Individual participant data sharing plan will be completed by the time of completion of the study
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing a Methodology to Assess 8-aminoquinoline Associated Haemolytic Risk in Females Heterozygous for G6PD in Endemic Populations
- ClinicalTrials.gov ID
- NCT03337152
- Acronym / sponsor ID
- 856370-2
- Conditions
- Malaria, Vivax, G6PD Deficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: study met study halting rules
- Enrolment
- 54 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- Mahidol Oxford Tropical Medicine Research Unit
- Study start
- 7 May 2018 (actual)
- Primary completion
- 21 Aug 2018 (actual)
- Study completion
- 21 Oct 2018 (actual)
- First posted
- 8 Nov 2017 (actual)
- Results
- Posted 12 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A clinical study designed to develop and inform an individual risk of hemolysis model based on individual red blood cell G6PD levels. Volunteers who are eligible to treatment with primaquine as per national guidelines and with confirmed normal G6PD levels as per the fluorescent spot test will be exposed to treatment regimens of either primaquine alone for 14 days or 3 day chloroquine with concomitant primaquine for 14 days. The volunteers will be followed intensively during treatment and for 14 days after treatment for haematologic measures, G6PD quantification, and drug level assays.
Detailed description
Open label, randomized trial with 72 total participants assigned to one of two treatment arms. Each arm will have 36 participants comprised of 12 males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD with a normal fluorescent spot test (FST) (G6PD genotype abnormal with G6PD activity ≥40% and ≤80% of normal). Arm 1a will receive primaquine for 14 days, and Arm 1b will receive chloroquine for 3 days and concomitant primaquine for 14 days. All participants will be healthy volunteers without severe G6PD deficiency who will be followed for two weeks after completing their study drug dosing. Pregnant women and those breastfeeding will be excluded. Venous blood samples will be taken at regular intervals for haematologic measures, G6PD quantification, and drug level assays. G6PD levels will be measured both by spectrophotometry to provide whole blood G6PD levels normalized for hemoglobin, as well by flow cytometry to to provide red blood cell G6PD distributions throughout the treatment and post treatment. Changes in the G6PD distributions will be modeled, incorporating other critical haematological indicators collected throughout the study too.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be randomized into one of two arms. 1a will receive primaquine for 14 days, and Arm 1b will receive chloroquine for 3 days and concomitant primaquine for 14 days.
| Arm | Type | Receives |
|---|---|---|
| 1A: primaquine | Other | Drug: primaquineTwelve males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD deficiency will be randomized to arm 1A. Participants in arm 1A will receive primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed. |
| 1B: chloroquine + primaquine | Other | Drug: chloroquine + primaquineTwelve males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD deficiency will be randomized to arm 1B. Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Previous G6PD test at Shoklo Malaria Research Unit (SMRU) clinic with one of following results: 1) G6PD homozygous wildtype females (G6PD genotype normal) 2) G6PD heterozygous females with a normal FST (G6PD genotype abnormal with G6PD activity ≥40% and ≤80% of normal ) 3) G6PD hemizygous wildtype males (G6PD genotype normal)
- Willing to participate and sign informed consent form
- Willing to allow donated samples to be used in future research
- Aged ≥18 years
- Ability (in the investigators' opinion) and willing to comply with all study requirements
Key exclusion criteria (11 listed)
- Malaria or other illness
- Recent history (within 20 days) of anti-malarial treatment
- History of allergy or adverse reaction to chloroquine or primaquine
- Blood transfusion in the past 3 months
- G6PD activity less than 40% normal activity or 3.00 IU/gHb by the quantitative G6PD spectrophotometric assay
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 |
|---|---|---|
| primaquineParticipants receive primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed. | Drug | 1A: primaquine |
| chloroquine + primaquineParticipants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed. | Drug | 1B: chloroquine + primaquine |
Primary outcome
Change in Haemoglobin
Time frame: 28 days after enrollment
The change in haemoglobin from baseline on exposure to primaquine for P.vivax treatment over treatment course to hemoglobin level at day 28.
Change in G6PD Concentration
Time frame: 28 days after enrollment
The haemoglobin-related change in G6PD concentration, as determined by spectrometer, over treatment course. Change is determined from baseline to day 28
5 secondary outcomes
Significance of CYP2D6
Time frame: 28 days after enrollment
Association of Drug Levels
Time frame: Days 1,2,3,5,7,9,11,14,17,21
Serious Adverse Events
Time frame: 28 days after enrollment
Significance of Reticulocyte Count
Time frame: Days 1,2,3,5,7,9,11,14,17,21
Significance of Urobilinogen Levels
Time frame: Days 1,2,3,5,7,9,11,14,17,21
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. Individual participant data sharing plan will be completed by the time of completion of the study
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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.
François Nosten, MD, PhD principal investigator
Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing primaquine and chloroquine + primaquine in people with Malaria, Vivax and G6PD Deficiency, run by PATH at 1 site in Thailand.
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 11 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: stopped early, as of the sponsor's last update on 12 Nov 2021. 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 Thailand. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Haemoglobin (time frame: 28 days after enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Nov 2021.