Ribavirin for Hemorrhagic Fever With Renal Syndrome in Germany

NCT00868946 | Withdrawn Phase 2

• 3 other identifiers: A-15314BAMC HUC C.2008.197USAMRIID HUC FY05-18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hemorrhagic Fever With Renal Syndrome

Keywords

Ribavirin; Hemorrhagic Fever with Renal Syndrome; Dobrava Virus; Puumala Virus

Outcome Measures

Primary Outcomes (2)

• Number of subject who develop oliguria

  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.

  5 years

• Number of mortalities

  5 years

Secondary Outcomes (1)

• Number and type of adverse events for all subjects.

  5 years

Study Arms (1)

Treatment with IND Ribavirin

EXPERIMENTAL

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)

Interventions

Virazole (Ribavirin) DRUG

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).

Also known as: Ribavirin

Treatment with IND Ribavirin

Eligibility Criteria

• Age: 17 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets the case definition for a probable or suspected case.
• Has read and signed the Informed Consent.
• Is at least 18 years of age (17, if active military) and not greater than 65 years of age.
• Has a blood sample drawn and a type and cross-match ordered for transfusion.
• Agrees to collection of required specimens.
• 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.
• 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.
• 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.
• 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.
• Has a hemoglobin of 10 g/dL or higher before starting IV Ribavirin.

You may not qualify if:

• Has know intolerance to Ribavirin
• Is pregnant
• 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).
• Has history of hemoglobinopathies (i.e., sickle-cell anemia or thalassemia major)
• Has history of autoimmune hepatitis
• Has a calculated serum creatinine clearance of \< 20 mL/min
• Has hemoglobin less than 10 g/dL that cannot be corrected to 10 g/dL before initiation of IV Ribavirin.
• Is considered as New York Heart Association Cardiac functional capacity of Class II or greater for ASHD and CHF.
• 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.
• 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.
• Is currently being treated with Didanosine (ddI). DdI must be discontinued before starting IV Ribavirin.
• History of gout or tophaceous gout
• Use of drugs known to result in bradyarrhythmias (certain betablockers and calcium channel blockers)
• Creatinine clearance of 20 to 30 mL/min

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead

Study Sites (1)

Landstuhl Regional Medical Center

Landstuhl, APO AE, 09180, Germany

Location

MeSH Terms

Conditions

Hemorrhagic Fever with Renal Syndrome

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Hantavirus Infections; Bunyaviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Elizabeth Rini

  Landstuhl Regional Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2009
• First Posted: March 25, 2009
• Study Start: October 1, 2009
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: January 2, 2020

Record last verified: 2019-12

Locations

DE (1)