Ignite Creation Date:
2024-05-05 @ 4:38 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00284687
Status:
COMPLETED
Last Update Posted:
2010-06-10
First Post:
2006-01-31
Brief Title:
Artesunate in Preemptive Treatment of Human Cytomegalovirus CMV in Stem Cell Transplant Recipients
Sponsor:
Hadassah Medical Organization
Organization:
Hadassah Medical Organization
Study Overview
Official Title:
Phase III Study Evaluating the Safety and Efficacy of Artesunate in Preemptive Treatment of Human Cytomegalovirus Disease in Stem Cell Transplant Recipients
Status:
COMPLETED
Status Verified Date:
2009-08
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:
Human cytomegalovirus HCMV has remained a major cause of morbidity and mortality following allogeneic bone marrow or peripheral blood stem cell transplantation SCT The most reliable virological predictive marker for disease development is the presence of HCMV viremia It has been further recognized that viral load and viral load kinetics are important determinants of pathogenesis Prior to the preventive use of antiviral agents CMV disease occurred in 15-45 of at-risk patients and carried a high mortality rate In the last decade major advances in the prevention of CMV disease have occurred with the application of pp65 antigenemia and qualitativequantitative polymerase chain reaction PCR assays for the rapid and sensitive diagnosis of HCMV infection combined with preemptive antiviral treatment targeted to patients with viremia The prevalence of early CMV disease has declined to 3 to 6 with intense antiviral drug use All antiviral drugs currently used for the treatment of systemic HCMV infection including ganciclovir foscarnet and cidofovir target the HCMV DNA polymerase Ganciclovir is the most widely used drug for preemptive treatment However ganciclovir treatment is often complicated by bone marrow toxicity with the occasional development of potentially life-threatening thrombocytopenia granulocytopenia and graft failure associated with secondary bacterial and fungal infection Another limitation of preemptive ganciclovir therapy is the requirement for intravenous administration The currently available oral valganciclovir is not yet approved for preemptive therapy in SCT recipients and is associated with high treatment cost Additionally prolonged or repeated ganciclovir treatment may lead to the development of drug resistance The use of foscarnet and cidofovir is limited by considerable nephrotoxicity low oral bioavailability and high cost Thus there is an increasing need for new effective non-toxic low-cost anti-HCMV drugs with high oral bioavailability
Recently the anti-malaria drug artesunate which is widely used in the treatment of severe malaria has been shown to be a highly effective inhibitor of HCMV in vitro Artesunate exhibited similar antiviral activity same micromolar range to that of ganciclovir while demonstrating no cytotoxicity Importantly its antiviral activity has been further demonstrated in vivo in a rat CMV model No significant side effects were demonstrated in a number of pre-clinical and clinical studies and artemisinin and its derivatives have been shown to be well-tolerated and safe in adults and children Several million people have taken artemisinins to date with no significant adverse or treatment-limiting effects being reported Although neurotoxicity has been reported with supraphysiological doses in animals it has not been documented in humans Meta-analyses of malaria patients treated with artemisinins demonstrated that this drug class is safe In rare cases however slight changes to haematology values have been seen including a reduction in the number of reticulocytes as well as a slight increase in transaminase levels These signs however do not generally give rise to any noticeable clinical manifestations In rare cases a slight but transient reduction in sinus heart rate has been observed Abdominal cramps and mild diarrhoea have been reported at elevated doses
Thus one might expect a similarly high degree of safety for the potential use of artesunate as an antiviral drug for HCMV infection Thus oral therapy with artesunate could be a beneficial option to the current therapies for the preemptive treatment of HCMV disease in SCT recipients
Recently the anti-malaria drug artesunate which is widely used in the treatment of severe malaria has been shown to be a highly effective inhibitor of HCMV in vitro Artesunate exhibited similar antiviral activity same micromolar range to that of ganciclovir while demonstrating no cytotoxicity Importantly its antiviral activity has been further demonstrated in vivo in a rat CMV model No significant side effects were demonstrated in a number of pre-clinical and clinical studies and artemisinin and its derivatives have been shown to be well-tolerated and safe in adults and children Several million people have taken artemisinins to date with no significant adverse or treatment-limiting effects being reported Although neurotoxicity has been reported with supraphysiological doses in animals it has not been documented in humans Meta-analyses of malaria patients treated with artemisinins demonstrated that this drug class is safe In rare cases however slight changes to haematology values have been seen including a reduction in the number of reticulocytes as well as a slight increase in transaminase levels These signs however do not generally give rise to any noticeable clinical manifestations In rare cases a slight but transient reduction in sinus heart rate has been observed Abdominal cramps and mild diarrhoea have been reported at elevated doses
Thus one might expect a similarly high degree of safety for the potential use of artesunate as an antiviral drug for HCMV infection Thus oral therapy with artesunate could be a beneficial option to the current therapies for the preemptive treatment of HCMV disease in SCT recipients
Detailed Description:
None
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