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: August 19, 2016
Last verified: August 2016
  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:
  • Number of subject who develop oliguria [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Number of subject who develop oliguria (≤ 400 mL of urine in a 24-hour period), who require hemodialysis, who have cardiac arrhythmias, or who experience severe hemorrhage [results in hypotension (< 90 mm Hg systolic blood pressure) or hemorrhagic shock]. Subject mortality will be evaluated.

  • Number of mortalities [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number and type of adverse events for all subjects. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: October 2009
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: November 2016 (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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   17 Years to 65 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Meets the case definition for a probable or suspected case.
  2. Has read and signed the Informed Consent.
  3. Is at least 18 years of age (17, if active military) and not greater than 65 years of age.
  4. Has a blood sample drawn and a type and cross-match ordered for transfusion.
  5. Agrees to collection of required specimens.
  6. Agrees to report any Adverse Event, Serious and Unexpected Adverse Events which may or may not be associated with administration of the drug for the duration of the study.
  7. Agrees to a follow-up visit and to donate blood and urine specimens at day 10, day 14 and between days 28 and 60 after their first dose of IV Ribavirin and to all follow-up visits for anemia or other medical conditions as required by the attending physician.
  8. Woman of childbearing age has a negative pregnancy test and agrees not to become pregnant during treatment and for 7 months after receiving Ribavirin. Treatment will be a maximum of 25 doses given over a one week time period. At least two reliable forms of effective contraception, including one barrier method, must be utilized during treatment and during the 7 months post-treatment period.
  9. Man agrees not to have intercourse with a pregnant woman during treatment and for 7 months after receiving Ribavirin, and take precautions to avoid producing pregnancies in female partners during and for 7 months after receiving Ribavirin.

    Treatment will be a maximum of 25 doses given over a one week time period. At least two reliable forms of effective contraception, including one barrier method, must be utilized during the treatment and during the 7 month post-treatment period.

  10. Has a hemoglobin of 10 g/dL or higher before starting IV Ribavirin.

Exclusion Criteria:

  1. Has know intolerance to Ribavirin
  2. Is pregenat
  3. Is irreversibly ill on presentation, as defined by presence of profound shock (shock which does not respond to supportive therapy within 3 hours after admission).
  4. Has history of hemoglobinopathies (i.e., sickle-cell anemia or thalassemia major)
  5. Has history of autoimmune hepatitis
  6. Has a calculated serum creatinine clearance of < 20 mL/min
  7. Has hemoglobin less than 10 g/dL that cannot be corrected to 10 g/dL before initiation of IV Ribavirin.
  8. Is considered as New York Heart Association Cardiac functional capacity of Class II or greater for ASHD and CHF.
  9. Has known cardiac conduction defects that may predispose to arrhythmias such as Wolfe-Parkinson-White Syndrome (WPW); or a history of bradyarrhythmias such as sick sinus syndrome or second degree heart block and no pacemaker.
  10. Has 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). If an individual develops heart rate of less than 35 beats per minute while on IV Ribavirin, the IV Ribavirin may be discontinued by the physician.
  11. Is currently being treated with Didanosine (ddI). DdI must be discontinued before starting IV Ribavirin.

Relative exclusion criteria:

  1. History of gout or tophaceous gout
  2. Use of drugs known to result in bradyarrhythmias (certain betablockers and calcium channel blockers)
  3. Creatinine clearance of 20 to 30 mL/min
  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: Elizabeth Rini Landstuhl Regional Medical Center
  More Information

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: August 19, 2016
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:
Syndrome
Fever
Hemorrhagic Fevers, Viral
Hemorrhagic Fever with Renal Syndrome
Disease
Pathologic Processes
Body Temperature Changes
Signs and Symptoms
RNA Virus Infections
Virus Diseases
Hantavirus Infections
Bunyaviridae Infections
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 25, 2016