Ignite Creation Date:
2024-05-05 @ 6:38 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00522132
Status:
COMPLETED
Last Update Posted:
2011-09-16
First Post:
2007-08-28
Brief Title:
Phase II Artesunate Study in Severe Malaria
Sponsor:
Medicines for Malaria Venture
Organization:
Medicines for Malaria Venture
Study Overview
Official Title:
Phase II Randomized Double-Blind Study of the Efficacy Safety Tolerability and Pharmacokinetics of Intravenous Artesunate in Children With Severe Malaria
Status:
COMPLETED
Status Verified Date:
2011-09
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:
The primary objective of the study is to evaluate the effectiveness of 2 intravenous artesunate dosing regimens 24 mgkg initially and at 12 24 48 and 72 hours or 40 mgkg initially and at 24 and 48 hours in clearing P falciparum parasites in children with severe malaria
Secondary objectives include
To compare the tolerability and safety of the 2 intravenous artesunate dosing regimens
To evaluate differences in the pharmacokinetic profile of intravenous artesunate by patient age and clinical presentation
Secondary objectives include
To compare the tolerability and safety of the 2 intravenous artesunate dosing regimens
To evaluate differences in the pharmacokinetic profile of intravenous artesunate by patient age and clinical presentation
Detailed Description:
This is a Phase II double-blind multicenter randomized parallel-group study of the antimalarial activity and safety of 2 intravenous artesunate regimens in children with severe P falciparum malaria Appendix B It will compare the efficacy safety and tolerability of the SEAQUAMAT regimen the recommended dosing regimen for adults8 which requires twice daily artesunate dosing on the first day to a simpler once daily regimen The study will also evaluate the pharmacokinetic profile of artesunate in pediatric patients
Prior to study initiation the protocol will be approved by the Independent Ethics CommitteeInstitutional Review Boards IECIRB of each site and the national regulatory authority of each study site
Approximately 200 patients will be randomized at 3 study sites in Africa which are part of the Severe Malaria in African Children SMAC network Patients will be randomized to 1 of 2 treatment cohorts
Cohort 1 artesunate 24 mgkg initially and at 12 24 48 and 72 hours 12 mgkg total dose or
Cohort 2 artesunate 4 mgkg initially and at 24 and 48 hours 12 mgkg total dose normal saline will be administered as a placebo at 12 and 72 hours in order to maintain the study blind
The study is divided into 3 main periods including the Pre-Treatment Period ScreeningDay 0 the Treatment Period Days 0 through 3 Day 0 is the first day of study drug dosing and the Post-Treatment Period including evaluations on Days 7 14 and 28 Children presenting to the study hospitals with signssymptoms of severe malaria will be screened for study enrollment Those with presumed severe malaria will be identified and informed consent for participation from parentsguardians will be obtained while confirmation of malaria is determined by microscopic analysis of a Giemsa-stained thick smear Patients who meet study inclusion criteria and none of the exclusion criteria will be randomized and promptly treated with 1 of the artesunate regimens while hospitalized for at least 4 days Days 0 1 2 and 3 Adjunctive therapy including fluids glucose and blood will follow SMAC standards based on WHO guidelines for the treatment of severe malaria Appendix C As soon as the patient is able to receive oral medication and no signs and symptoms of severe malaria are present but not before the last pharmacokinetic sample is taken approximately 50 hours after the start of therapy a single dose of sulfadoxinepyrimethamine will be administered to ensure parasitological cure Patients who received sulfadoxinepyrimethamine within 14 days prior Study Day 0 will receive mefloquine instead of SP to ensure effective parasitological cure
If the parasitemia is controlled and the safety laboratory tests from Day 3 indicate no clinical concern warranting prolonged hospitalization the patient may be discharged at the discretion of the investigator If a patient is discharged from the hospital on Day 3 heshe will return to the study site on Day 7 for evaluation If the patient is unable to tolerate oral liquids or food within 6-24 hours after the last dose of artesunate the patient will continue to be hospitalized and treated with parenteral antimalarial therapy until heshe is able to resume oral intake or a total of 7 days of therapy have been completed All patients will return to the study site for evaluation on Days 14 and 28 to assess resolution of clinical complications and monitor for safety of therapy
Efficacy will be assessed by various parasite clearance parameters Safety evaluations including physical examinations vital signs hematology and chemistry laboratory parameters and monitoring of adverse events will be performed throughout the study Pharmacokinetic assessments will be performed at 3 different timepoints during the study
If adverse events reported during the study are unresolved by Day 28 patients will be followed for an additional 30 days or until resolution of the event or determination that no further medical management is deemed necessary Similarly the investigator will instruct the parentsguardians to return the patient to the study site if any untoward event occurs within 30 days of completing study drug
Prior to study initiation the protocol will be approved by the Independent Ethics CommitteeInstitutional Review Boards IECIRB of each site and the national regulatory authority of each study site
Approximately 200 patients will be randomized at 3 study sites in Africa which are part of the Severe Malaria in African Children SMAC network Patients will be randomized to 1 of 2 treatment cohorts
Cohort 1 artesunate 24 mgkg initially and at 12 24 48 and 72 hours 12 mgkg total dose or
Cohort 2 artesunate 4 mgkg initially and at 24 and 48 hours 12 mgkg total dose normal saline will be administered as a placebo at 12 and 72 hours in order to maintain the study blind
The study is divided into 3 main periods including the Pre-Treatment Period ScreeningDay 0 the Treatment Period Days 0 through 3 Day 0 is the first day of study drug dosing and the Post-Treatment Period including evaluations on Days 7 14 and 28 Children presenting to the study hospitals with signssymptoms of severe malaria will be screened for study enrollment Those with presumed severe malaria will be identified and informed consent for participation from parentsguardians will be obtained while confirmation of malaria is determined by microscopic analysis of a Giemsa-stained thick smear Patients who meet study inclusion criteria and none of the exclusion criteria will be randomized and promptly treated with 1 of the artesunate regimens while hospitalized for at least 4 days Days 0 1 2 and 3 Adjunctive therapy including fluids glucose and blood will follow SMAC standards based on WHO guidelines for the treatment of severe malaria Appendix C As soon as the patient is able to receive oral medication and no signs and symptoms of severe malaria are present but not before the last pharmacokinetic sample is taken approximately 50 hours after the start of therapy a single dose of sulfadoxinepyrimethamine will be administered to ensure parasitological cure Patients who received sulfadoxinepyrimethamine within 14 days prior Study Day 0 will receive mefloquine instead of SP to ensure effective parasitological cure
If the parasitemia is controlled and the safety laboratory tests from Day 3 indicate no clinical concern warranting prolonged hospitalization the patient may be discharged at the discretion of the investigator If a patient is discharged from the hospital on Day 3 heshe will return to the study site on Day 7 for evaluation If the patient is unable to tolerate oral liquids or food within 6-24 hours after the last dose of artesunate the patient will continue to be hospitalized and treated with parenteral antimalarial therapy until heshe is able to resume oral intake or a total of 7 days of therapy have been completed All patients will return to the study site for evaluation on Days 14 and 28 to assess resolution of clinical complications and monitor for safety of therapy
Efficacy will be assessed by various parasite clearance parameters Safety evaluations including physical examinations vital signs hematology and chemistry laboratory parameters and monitoring of adverse events will be performed throughout the study Pharmacokinetic assessments will be performed at 3 different timepoints during the study
If adverse events reported during the study are unresolved by Day 28 patients will be followed for an additional 30 days or until resolution of the event or determination that no further medical management is deemed necessary Similarly the investigator will instruct the parentsguardians to return the patient to the study site if any untoward event occurs within 30 days of completing study drug
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EDCTP Grant 200401Md2 | None | None | None |