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Trial record 3 of 6 for:    Aminoquinolines

Assessing a Risk Model for G6PD Deficiency

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ClinicalTrials.gov Identifier: NCT03337152
Recruitment Status : Suspended (study met study halting rules)
First Posted : November 8, 2017
Last Update Posted : May 23, 2019
Sponsor:
Collaborator:
Mahidol Oxford Tropical Medicine Research Unit
Information provided by (Responsible Party):
PATH

Tracking Information
First Submitted Date  ICMJE October 27, 2017
First Posted Date  ICMJE November 8, 2017
Last Update Posted Date May 23, 2019
Actual Study Start Date  ICMJE May 7, 2018
Estimated Primary Completion Date December 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2017)
  • absolute haemoglobin drop [ Time Frame: 28 days after enrollment ]
    The absolute haemoglobin reduction from baseline on exposure to primaquine for P.vivax treatment over treatment course.
  • change in intracellular G6PD concentration [ Time Frame: 28 days after enrollment ]
    The absolute reduction in haemoglobin-related change in intracellular G6PD concentration profiles over treatment course.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03337152 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2017)
  • significance of CYP2D6 [ Time Frame: 28 days after enrollment ]
    relevance of Dextromethorphan assay results to risk of haemolysis models
  • association of drug levels [ Time Frame: Days 1,2,3,5,7,9,11,14,17,21 ]
    Association of chloroquine and primaquine drug levels at the time of sampling for haematological and G6PD profiles.
  • adverse events [ Time Frame: 28 days after enrollment ]
    frequency of adverse events in in women heterozygous for G6PD
  • significance of reticulocyte count [ Time Frame: Days 1,2,3,5,7,9,11,14,17,21 ]
    relevance of reticulocyte count to risk of haemolysis models
  • significance of urobilinogen levels [ Time Frame: Days 1,2,3,5,7,9,11,14,17,21 ]
    relevance of urobilinogen tests to risk of haemolysis models
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessing a Risk Model for G6PD Deficiency
Official Title  ICMJE Developing a Methodology to Assess 8-aminoquinoline Associated Haemolytic Risk in Females Heterozygous for G6PD in Endemic Populations
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Condition  ICMJE
  • Malaria, Vivax
  • G6PD Deficiency
Intervention  ICMJE
  • Drug: primaquine
    Participants receive primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed.
  • Drug: chloroquine + primaquine
    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 Arms  ICMJE
  • 1A: primaquine
    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.
    Intervention: Drug: primaquine
  • 1B: chloroquine + primaquine
    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.
    Intervention: Drug: chloroquine + primaquine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: November 6, 2017)
72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date December 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03337152
Other Study ID Numbers  ICMJE 856370-2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Individual participant data sharing plan will be completed by the time of completion of the study
Responsible Party PATH
Study Sponsor  ICMJE PATH
Collaborators  ICMJE Mahidol Oxford Tropical Medicine Research Unit
Investigators  ICMJE
Principal Investigator: François Nosten, MD, PhD Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit
PRS Account PATH
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP