Ignite Creation Date:
2024-05-05 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00158587
Status:
COMPLETED
Last Update Posted:
2017-01-12
First Post:
2005-09-09
Brief Title:
Eight Week Primaquine Regimen for the Treatment of Vivax Malaria
Sponsor:
London School of Hygiene and Tropical Medicine
Organization:
London School of Hygiene and Tropical Medicine
Study Overview
Official Title:
A Placebo Controlled Randomised Evaluation of an Eight Week Primaquine Regimen for the Treatment of Vivax Malaria
Status:
COMPLETED
Status Verified Date:
2017-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Plasmodium vivax represents a major health problem throughout the tropics Outside Africa it accounts for over 50 of cases affecting an estimated 70-80 million people per year A substantial proportion of clinical cases are not caused by infective bites of Anopheles spp but by activation of latent hypnozoites in the liver These relapses may significantly impede development since each illness may result in 5-15 days of absence from work or school
PrimaquinePQ is the only drug available that eliminates hypnozoites though its use is beset by clinical problems it may precipitate haemolytic anaemia in individuals deficient in the blood enzyme glucose 6 phosphate dehydrogenase G6PD Without affordable G6PD testing primaquine use is precluded Evidence suggests however that a course of 8 weekly doses may be a safe and effective alternative to the traditional 14 day course of the drug The aim of the proposed study therefore is to test whether 8 weekly doses of primaquine is as effective as the 14 day course at preventing relapse malaria without the risk of hemolysis in G6PD deficient individuals
PrimaquinePQ is the only drug available that eliminates hypnozoites though its use is beset by clinical problems it may precipitate haemolytic anaemia in individuals deficient in the blood enzyme glucose 6 phosphate dehydrogenase G6PD Without affordable G6PD testing primaquine use is precluded Evidence suggests however that a course of 8 weekly doses may be a safe and effective alternative to the traditional 14 day course of the drug The aim of the proposed study therefore is to test whether 8 weekly doses of primaquine is as effective as the 14 day course at preventing relapse malaria without the risk of hemolysis in G6PD deficient individuals
Detailed Description:
Old evidence suggests that successful PQ therapy is not a function of the length of the course of treatment nor the circulating concentration of the drug but of the total dosage administered The same dose administered over 7 days 14 days and 8 weeks equally prevented relapse in vivax malaria The hemolysis seen in shorter courses is often self-limiting suggesting that feedback mechanisms up-regulate production of red cells in response to haemolytic challenge The proposed extended course is likely to be well tolerated in G6PD deficient individuals as a result of these safeguards especially in this population which has been exposed to the 5 day PQ regimen for a number of years without reported adverse effects
The aim of the study therefore is to test whether an 8 week regimen proves effective without the associated risk of haemolysis in G6PD deficient individuals However operational concerns remain about adherence to this protracted treatment regimen Therefore we will compare the 8 week course in 2 different groups the first to be directly observed dosing the second to be unsupervised dosing using pre-packaged foil wrapped PQ in appropriately labelled individual boxes supplied with strong health education messages This would be appropriate for deployment in a resource-poor setting if it proved effective and safe
Objectives
To evaluate whether an eight week primaquine regimen using single weekly doses can provide adequate radical cure of vivax malaria under experimental and operational conditions and is safe in and acceptable to a population with glucose 6 phosphate dehydrogenase deficiency The specific objectives of the study are set out below
1 Determine the efficacy of an eight-week primaquine regime using single weekly doses in preventing relapses of P vivax infections following supervised versus unsupervised administration of the drug
2 Compare the efficacy and operational aspects eg adherence between the two week eight week supervised and eight week blister package regimes
3 Monitoring of the effect of 8 week PQ on G6PD deficient individuals
4 Examine the user acceptability and economic advantages of this course of treatment
Study population
Vivax positive individuals from Adizai and Baghicha refugee camps Pakistan and Jalalabad Afghanistan
Laboratory Examination
All suspected malaria cases attending basic health units will have thick and thin blood films taken and examined by conventional light microscopy Cases diagnosed with P vivax infection will be asked to participate in the study unless the exclusion criteria are met All patients will then be tested for G6PD deficiency by near patient testing The test is a colorimetric qualitative test for G6PD in red cells requiring 005 ml of blood In addition a filter paper blood spot will be collected to allow molecular typing of the parasite This will differentiate between a new and a relapse infection
Design
Randomised placebo controlled study comparing the following four study groups
1 Initial 3 day chloroquine with supervised weekly placebo for 8 weeks
2 Initial 3 day chloroquine followed by supervised 14 day primaquine treatment
3 Initial 3 day chloroquine followed by supervised 8 week primaquine treatment 45 mg week
All patients will be given health education messages and strongly advised to complete the course In addition a safety arm will be used for G6PD deficient patients this will be used to compare PCV with group 3 above This will be an 8 week regimen administered by direct observation and will receive close monitoring for haemolysis
Treatment
All patients will be given a full therapeutic course of chloroquine Primaquine will be administered to the study groups according to the respective protocol schedule All relapses and new cases will be re-treated using the same regime and procedure as at the time of admission
Monitoring
Patients in treatment groups 1 2 and 3 will be monitored for the initial 8 weeks of treatment for adverse events G6PD deficient patients will be monitored for signs of hemolysis every other day for the first 2 weeks of treatment and then once per week prior to dosing until completion of the course Following the treatment period patients will be monitored for 1 year for the following outcomes
Primary Efficacy Variable Proportion with relapses of P vivax in 12 months of follow-up
Secondary Efficacy Variables Time to subsequent relapse episode number of relapse episodes in 12 months side effects adverse events
Patients will be advised to return to the BHU in the event of recurrent symptoms within 12 months following enrolment to the study A patient will be deemed to have completed the study after 12 months of follow-up In any event each patient will be contacted once every 2 weeks during the follow-up period in order to collect relevant information At each episode a sample of blood will allow molecular typing of the parasite and define whether the patient has a new infection or a relapse
The aim of the study therefore is to test whether an 8 week regimen proves effective without the associated risk of haemolysis in G6PD deficient individuals However operational concerns remain about adherence to this protracted treatment regimen Therefore we will compare the 8 week course in 2 different groups the first to be directly observed dosing the second to be unsupervised dosing using pre-packaged foil wrapped PQ in appropriately labelled individual boxes supplied with strong health education messages This would be appropriate for deployment in a resource-poor setting if it proved effective and safe
Objectives
To evaluate whether an eight week primaquine regimen using single weekly doses can provide adequate radical cure of vivax malaria under experimental and operational conditions and is safe in and acceptable to a population with glucose 6 phosphate dehydrogenase deficiency The specific objectives of the study are set out below
1 Determine the efficacy of an eight-week primaquine regime using single weekly doses in preventing relapses of P vivax infections following supervised versus unsupervised administration of the drug
2 Compare the efficacy and operational aspects eg adherence between the two week eight week supervised and eight week blister package regimes
3 Monitoring of the effect of 8 week PQ on G6PD deficient individuals
4 Examine the user acceptability and economic advantages of this course of treatment
Study population
Vivax positive individuals from Adizai and Baghicha refugee camps Pakistan and Jalalabad Afghanistan
Laboratory Examination
All suspected malaria cases attending basic health units will have thick and thin blood films taken and examined by conventional light microscopy Cases diagnosed with P vivax infection will be asked to participate in the study unless the exclusion criteria are met All patients will then be tested for G6PD deficiency by near patient testing The test is a colorimetric qualitative test for G6PD in red cells requiring 005 ml of blood In addition a filter paper blood spot will be collected to allow molecular typing of the parasite This will differentiate between a new and a relapse infection
Design
Randomised placebo controlled study comparing the following four study groups
1 Initial 3 day chloroquine with supervised weekly placebo for 8 weeks
2 Initial 3 day chloroquine followed by supervised 14 day primaquine treatment
3 Initial 3 day chloroquine followed by supervised 8 week primaquine treatment 45 mg week
All patients will be given health education messages and strongly advised to complete the course In addition a safety arm will be used for G6PD deficient patients this will be used to compare PCV with group 3 above This will be an 8 week regimen administered by direct observation and will receive close monitoring for haemolysis
Treatment
All patients will be given a full therapeutic course of chloroquine Primaquine will be administered to the study groups according to the respective protocol schedule All relapses and new cases will be re-treated using the same regime and procedure as at the time of admission
Monitoring
Patients in treatment groups 1 2 and 3 will be monitored for the initial 8 weeks of treatment for adverse events G6PD deficient patients will be monitored for signs of hemolysis every other day for the first 2 weeks of treatment and then once per week prior to dosing until completion of the course Following the treatment period patients will be monitored for 1 year for the following outcomes
Primary Efficacy Variable Proportion with relapses of P vivax in 12 months of follow-up
Secondary Efficacy Variables Time to subsequent relapse episode number of relapse episodes in 12 months side effects adverse events
Patients will be advised to return to the BHU in the event of recurrent symptoms within 12 months following enrolment to the study A patient will be deemed to have completed the study after 12 months of follow-up In any event each patient will be contacted once every 2 weeks during the follow-up period in order to collect relevant information At each episode a sample of blood will allow molecular typing of the parasite and define whether the patient has a new infection or a relapse
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None