Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
NCT number |
NCT00623168 |
Other study ID # |
A-14474 |
Secondary ID |
TAMC HUC 23H07 |
Status |
Enrolling by invitation |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
February 2008 |
Est. completion date |
December 2021 |
Study information
Verified date |
February 2021 |
Source |
U.S. Army Medical Research and Development Command |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Hemorrhagic Fever with Renal Syndrome (HFRS) is caused by a virus acquired by contact with
chronically infected rodent hosts. HFRS is present throughout Korea. Treatment consists
mainly of supportive care with careful attention to control of blood pressure and fluid
balance and/or dialysis. Early initiation of IND Intravenous Ribavirin has been shown to be
an effective treatment for HFRS and may prevent the need for dialysis. It is important to
initiate therapy based on a diagnosis consistent with HFRS and a history that makes exposure
likely. This study will monitor the clinical events that occur with HFRS as well as the
safety and efficacy of Ribavirin.
Description:
Hemorrhagic Fever with Renal Syndrome (HFRS) is caused by viruses in the genus Hantavirus of
the family Bunyaviridae. There are four known Hantavirus that cause HFRS: Hantaan, Seoul,
Puumala and Dobrava viruses. HFRS is acquired by contact with chronically infected rodent
hosts, most commonly from inhalation of infected rodent excreta. Hemorrhagic fever with renal
syndrome is characterized clinically by the triad of fever, hemorrhage and renal
insufficiency. HFRS typically consists of five consecutive but frequently overlapping
clinical phases: febrile, hypotensive, oliguric, diuretic and convalescent. DoD operations
have resulted in the deployment of personnel in Europe and Southeast Asia, areas endemic for
HFRS, a viral hemorrhagic fever. Early initiation of therapy with intravenous Ribavirin has
been shown to be an effective treatment for HFRS. It is therefore important to initiate
therapy based on a clinical diagnosis consistent with viral hemorrhagic fever and with an
epidemiological history for risk of exposure to the hantavirus. Ribavirin is a nucleoside
(guanosine) analog with activity against a wide variety ribonucleic acid and deoxyribonucleic
acid viruses. Mechanism of action is not fully defined. The mechanism may be related to
alteration of cellular nucleotide pools and of viral messenger RNA formation, but recent data
suggest the mechanism of Ribavirin in HFRS may be to serve as a RNA virus mutagen resulting
in an "extinction catastrophe" error, as a result of incorporation in the viral RNA genome.
Ribavirin is licensed in the United States in aerosol form for the treatment of severe lower
respiratory tract infection in children and in the oral formulation in combination with
recombinant interferon alpha for the treatment of chronic hepatitis C infection. The
intravenous formulation of ribavirin in not licensed in the United States. IV Ribavirin for
the treatment of HFRS is used under IND 16,666.
This is a Phase 2, open-label study of the safety of IV Ribavirin treatment in individuals
with Hemorrhagic Fever with Renal Syndrome (HFRS) admitted to the 121st Combat Support
Hospital, Seoul, Republic of Korea. The study will also monitor morbidity and mortality of
subjects with HFRS who are treated with IV Ribavirin. The study population will include all
subjects with a probable or suspected clinical diagnosis of HFRS, at least 18 years of age
(age 17 if active military) but not greater than 65 years of age. The Investigators intend to
treat all individuals who present with a tentative diagnosis of HFRS (and within 7 days of
onset of illness) and meet entry criteria with a 7 day course of IV Ribavirin and a 28-60 day
follow up period after first dose of Ribavirin. In addition to treatment with Ribavirin, all
subjects will be given standard supportive and symptomatic care as determined by the clinical
judgment of attending physicians or consultants who manage the subject's care at the 121 CSH.
Up to 50 subjects could potentially be enrolled in a five year time period with an expected
accrual of 0-5 subjects per year, but the number may be higher (10 to 20 persons in a year)
if an HFRS outbreak should occur. Specific inclusion/exclusion/relative exclusion criteria
are a part of the protocol. Safety procedures required during 7 days of treatment include
continuous cardiac monitoring, daily lab work, physical exams and vital signs.