Ignite Creation Date:
2024-05-06 @ 8:00 AM
Last Modification Date:
2024-10-26 @ 11:54 AM
Study NCT ID:
NCT02640495
Status:
WITHDRAWN
Last Update Posted:
2018-08-22
First Post:
2015-11-16
Brief Title:
Artemisinin Resistance In Malaria Treated With IV Artesunate
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
A Multicenter Prospective Observational Study to Assess the Efficacy of Artesunate in Malaria Treated With Parenteral Artesunate in Areas With Artemisinin Resistance A Study by the Tracking Resistance to Artemisinin Collaboration TRAC
Status:
WITHDRAWN
Status Verified Date:
2018-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Due to the relative low incidence of severe malaria in Southeast Asia
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ARIMTIA
Brief Summary:
The spread of artemisinin resistant falciparum malaria presents new challenges to both the control and treatment of malaria Loss of ring stage susceptibility to the artemisinins might jeopardize the use of parenteral artesunate as the first line drug for the treatment of severe falciparum malaria
The purpose of this study is to assess the effect of artemisinin resistance defined by a Kelch13 mutation with known functional significance in P falciparum malaria requiring parenteral artesunate treatment on lactate clearance parameters
The purpose of this study is to assess the effect of artemisinin resistance defined by a Kelch13 mutation with known functional significance in P falciparum malaria requiring parenteral artesunate treatment on lactate clearance parameters
Detailed Description:
The investigators propose a multi-center observational study to assess the effect of artemisinin resistance as defined by the presence of relevant Kelch13 mutations on the efficacy of parenteral artesunate for the treatment of malaria stratified for disease severity on admission
The patients will receive the standard intravenous treatment for severe malaria parenteral artesunate Primary endpoints will be the plasma lactate concentration at 12 hours as a proportion of the plasma lactate at the start of treatment Secondary endpoints will be improvement of Glasgow or Blantyre Coma Scores and other indicators of neurological recovery or deterioration parasite clearance rates time until resolution of fever development of new severity or neurological signs under treatment development of severe anemia renal and hepatic injury total duration of hospitalization outcome of pregnancy in pregnant female patients mortality rates and the necessity to treat with antibiotics need for renal replacement therapy mechanical ventilation blood transfusion and rescue treatments
On admission blood will be taken for the determination of genetic markers of antimalarial resistance including Kelch13 mutations of known functional significance and in vitro sensitivity tests to artemisinins and other antimalarials Additional blood samples will be used for measuring plasma organic acid biomarkers of severe falciparum malaria measured by mass spectrometry Difference in the kinetics of these acids will be an additional endpoint Difference in the transcriptome of p falciparum will be assessed by RNA measurements at baseline and 3 timepoints during treatment
The proposed sites in Vietnam and Cambodia have been chosen based on the prevalence of artemisinin resistant falciparum malaria incidence of severe malaria and local experience in participating in clinical trials
Interim analysis
To ensure timely recognition of the effect of artemisinin resistance on the outcome in malaria treated with parenteral artesunate an interim analysis will be performed after the inclusion of 60 patients or one malaria transmission season whatever comes first An independent Data Safety Board will assess whether the difference in outcome between infections with artemisinin resistant versus sensitive strains warrants early termination and reporting of the study
The patients will receive the standard intravenous treatment for severe malaria parenteral artesunate Primary endpoints will be the plasma lactate concentration at 12 hours as a proportion of the plasma lactate at the start of treatment Secondary endpoints will be improvement of Glasgow or Blantyre Coma Scores and other indicators of neurological recovery or deterioration parasite clearance rates time until resolution of fever development of new severity or neurological signs under treatment development of severe anemia renal and hepatic injury total duration of hospitalization outcome of pregnancy in pregnant female patients mortality rates and the necessity to treat with antibiotics need for renal replacement therapy mechanical ventilation blood transfusion and rescue treatments
On admission blood will be taken for the determination of genetic markers of antimalarial resistance including Kelch13 mutations of known functional significance and in vitro sensitivity tests to artemisinins and other antimalarials Additional blood samples will be used for measuring plasma organic acid biomarkers of severe falciparum malaria measured by mass spectrometry Difference in the kinetics of these acids will be an additional endpoint Difference in the transcriptome of p falciparum will be assessed by RNA measurements at baseline and 3 timepoints during treatment
The proposed sites in Vietnam and Cambodia have been chosen based on the prevalence of artemisinin resistant falciparum malaria incidence of severe malaria and local experience in participating in clinical trials
Interim analysis
To ensure timely recognition of the effect of artemisinin resistance on the outcome in malaria treated with parenteral artesunate an interim analysis will be performed after the inclusion of 60 patients or one malaria transmission season whatever comes first An independent Data Safety Board will assess whether the difference in outcome between infections with artemisinin resistant versus sensitive strains warrants early termination and reporting of the study
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