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Ribavirin for Hemorrhagic Fever With Renal Syndrome in Germany (HFRS)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT00868946
First received: March 24, 2009
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

This is a treatment protocol using IND Ribavirin-there is no control group. Hemorrhagic Fever with Renal Syndrome (HFRS) is caused by a virus acquired by contact with chronically infected rodent hosts. HFRS is present throughout Europe and caused mainly by Puumala and Dobrava viruses. 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 (determination if the disease is caused by Puumala or Dobrava virus is helpful) 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.


Condition Intervention Phase
Hemorrhagic Fever With Renal Syndrome
Drug: Virazole (Ribavirin)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Treatment Protocol of Intravenous Ribavirin in Adult Subjects With Hemorrhagic Fever With Renal Syndrome (HFRS) in Landstuhl Regional Medical Center (Landstuhl, Germany) IND 16,666

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • To monitor the morbidity (clinical events that occur with HFRS including oliguria, dialysis requirement, cardiac arrhythmias, and severe hemorrhage) and mortality of the subjects with HFRS who are treated with IV Ribavirin. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the safety of IV Ribavirin treatment in subjects with a probable or suspected case of hemorrhagic fever with renal syndrome (HFRS). [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: October 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment with IND Ribavirin
All consented subjects who meet all inclusion and no exclusion criteria will enter this open label protocol and be treated with IND Virazole (Ribavirin) for 7 days with multiple dosing regime based on weight and dosage day.
Drug: Virazole (Ribavirin)

Duration of Subject Participation:7-day course of treatment with follow-up 28 - 60 days after first dose of IV ribavirin Route of Administration and Regimen:The drug is administered IV in a volume of 50-100 mL of normal saline to be infused over 30-40 minutes.

Ribavirin Loading dose, 33 mg/kg (maximum dose: 2.64 g), followed by a dose of 16 mg/kg (maximum dose: 1.28 g) every 6 hours for the first 4 days (15 doses), and 8 mg/kg (maximum dose: 0.64 g) every 8 hours for the subsequent 3 days (9 doses).

Other Name: Ribavirin

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  Eligibility

Ages Eligible for Study:   17 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Subjects will be enrolled in this study if they:

  • Have read and signed the Informed Consent
  • Are at least 18 years of age (17, if active military) and not greater than 65 years of age.
  • Meet the case definition for a probable or suspected case.
  • Have a blood sample drawn and a type and cross-match ordered for transfusion.
  • Agree to collection of required specimens.
  • Agree to report any Adverse Events, Serious and Unexpected Adverse Events for the duration of the study.
  • Agree to a follow-up visit and to donate blood and urine specimens at day 10, day 14 and between days 28 and 60 after the first dose of IV Ribavirin and to all follow-up visits for anemia or other medical conditions as required by the attending physician.
  • Women of childbearing age must have a negative pregnancy test and agree not to become pregnant during treatment and for 7 months after receiving Ribavirin. Women will be counseled concerning the risks of IV Ribavirin.
  • Men agree not to have intercourse with pregnant women during treatment and for 7 months after receiving Ribavirin, and take precautions to avoid producing pregnancies during treatment and for 7 months after receiving Ribavirin.
  • Have a hemoglobin greater than or equal to 10 g/dL before starting IV Ribavirin.

Exclusion Criteria: Individuals will not be enrolled in the study if they have:

  • A known intolerance to Ribavirin.
  • Are irreversibly ill on presentation, as defined by presence of profound shock, which does not respond to supportive therapy within 3 hours after admission.
  • A positive pregnancy test.
  • An estimated creatinine clearance < 20 ml/minute.
  • A history of hemoglobinopathies (i.e., sickle-cell anemia or thalassemia major).
  • A history of autoimmune hepatitis.
  • A hemoglobin less than 10 g/dL that cannot be corrected to ≥10 g/dL before initiation of IV Ribavirin.
  • A New York Heart Association Cardiac functional capacity of Class II or greater for ASHD and CHF.
  • Known cardiac conduction defects that may predispose the subject to arrhythmias, such as second or third degree heart block or sick sinus syndrome (and no pacemaker), or Wolfe-Parkinson-White Syndrome.
  • A sinus bradycardia of less than 40 beats per minute (or sinus bradycardia less than 50 beats per minute if the individual is not known to have a low resting heart rate related to physical conditioning).
  • Concurrent therapy with Didanosine (ddI). DdI must be discontinued before starting the IV Ribavirin.

Relative Exclusion Criteria: The PI should make the decision concerning enrollment of subjects with relative exclusion criteria based on risk versus benefit of the drug.

  • Creatinine clearance is 20 - 30 mL/minute
  • History of gout or tophaceous gout
  • On any drug that may decrease heart rate (beta-blockers, calcium channel blockers, digoxin IV Ribavirin should be avoided in severe renal insufficiency, and its use with a creatinine clearance between 20 to 30 mL/min should be based on the risk versus benefit. If used, the drug should be discontinued if the creatinine clearance decreases to 20 mL/min or lower.

Uric acid levels are elevated in 85% of individuals with HFRS (levels often > 10 U/ml in prior patients on the protocol). However, there is no data that IV Ribavirin causes increased uric acid or potentiates gout.

Due to both bradycardia and anemia associated with HFRS, it is recommended that drugs known to decrease the heart rate be held, if possible, while on IV Ribavirin therapy.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868946

Locations
Germany
Landstuhl Regional Medical Center
Landstuhl, APO Ae, Germany, 09180
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Mary Hinkle, MD Landstuhl Regional Medical Center
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT00868946     History of Changes
Other Study ID Numbers: A-15314, BAMC HUC C.2008.197, USAMRIID HUC FY05-18
Study First Received: March 24, 2009
Last Updated: March 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
Ribavirin
Hemorrhagic Fever with Renal Syndrome
Dobrava Virus
Puumala Virus

Additional relevant MeSH terms:
Hantavirus Infections
Fever
Hemorrhagic Fever with Renal Syndrome
Hemorrhagic Fevers, Viral
Syndrome
Body Temperature Changes
Bunyaviridae Infections
Disease
Pathologic Processes
RNA Virus Infections
Signs and Symptoms
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014