Treatment of Hemorrhagic Fever With Ribavirin

Brief Title

Treatment of Hemorrhagic Fever With Ribavirin

Official Title

Treatment Protocol for Adults With Hemorrhagic Fever With Renal Syndrome (HFRS) With Intravenous (IV) Ribavirin

Brief Summary

      Multisite protocol to provide IV Ribavirin treatment to patients with probable or suspected
      case of Hemorrhagic Fever with Renal Syndrome (HFRS)
    

Detailed Description

      This protocol is an open-label, single-arm, multisite protocol to provide IV ribavirin
      treatment to patients with probable or suspected case of HFRS. Individuals with a tentative
      diagnosis of HFRS will be admitted to the MTF and treated for up to 7 days with doses of IV
      ribavirin.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Reduction in Mortality with IV Ribavirin at 10days

Secondary Outcome

 Reported Adverse Events

Condition

Hemorrhagic Fever

Intervention

Virazole

Study Arms / Comparison Groups

 Efficacy of IV Ribavirin
Description:  The proposed clinical dose is based on drug dosage used in the HFRS clinical trial in China that demonstrated efficacy: 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).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

50

Start Date

June 2021

Completion Date

July 2022

Primary Completion Date

April 2022

Eligibility Criteria

        Inclusion Criteria:

        A subject must meet all of the following criteria to be included in the study:

          -  Meets the protocol case definition for a probable or suspected case (see Section 8.5.2
             and Section 8.5.3)

          -  Has read and signed the Informed Consent.

          -  Must be Department of Defense (DoD)-affiliated personnel including active and reserve
             component service members, US civilian employees, contractors, other US Personnel, and
             dependents as well as allied military forces and local nationals who have been granted
             access to the medical facility.

          -  Is at least 18 years of age (17, if active military) and not greater than 65 years of
             age.

          -  Agrees to have a blood sample drawn and a type and cross-match ordered for
             transfusion.

          -  Agrees to collection of required specimens.

          -  Agrees to report any adverse events (AEs) for the duration of the patient's treatment
             protocol participation.

          -  Agrees to follow-up visits and to donate blood and urine specimens at Day 10, Day 14,
             and once 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.

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

          -  Women who are breastfeeding agree to discontinue breastfeeding during treatment with
             IV ribavirin and during the 7-month post-treatment period.

          -  Woman of childbearing potential must have a negative pregnancy test within 24 hours
             before starting treatment and agrees not to become pregnant during treatment and for 7
             months after receiving IV ribavirin. Treatment will be a maximum of 25 doses given
             over a 1 week time period. At least 2 reliable forms of effective contraception,
             including 1 barrier method, must be utilized during treatment and during the 7 months
             post treatment period.(See Section 12.1.6 Pregnancy)

          -  Male subjects agree not to have intercourse with pregnant women during treatment and
             for 7 months after receiving IV 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 1 week time period. At least 2
             reliable forms of effective contraception, including 1 barrier method, must be
             utilized during the treatment and during the 7 month post-treatment period (See
             Section 12.1.6 Pregnancy). Their female partner should use a highly effective
             contraceptive method (see Section 12.1.6). They agree to use a male condom plus an
             additional method with a failure rate of < 1% per year).

        Exclusion Criteria:

        Individual will not be enrolled in the protocol if they meet any of the following criteria:

          -  Has a known intolerance to ribavirin.

          -  Is irreversibly ill on presentation, as defined by presence of profound shock, which
             does not respond to supportive therapy within 3 hours after admission.

          -  Has a positive pregnancy test.

          -  Has an estimated creatinine clearance < 20 mL/minute

          -  Is receiving renal dialysis.

          -  Has a history of hemoglobinopathies (ie, sickle-cell anemia or thalassemia major).

          -  Has a history of autoimmune hepatitis.

          -  Has a hemoglobin less than 10 g/dL that cannot be corrected to ≥ 10 g/dL before
             initiation of IV ribavirin.

          -  Has a New York Heart Association Cardiac functional capacity of Class II or greater
             for astherosclerotic heart diseases (ASHD) and congestive heart failure (CHF). Class
             II ASHD or greater includes angina that occurs at rest, with daily activities, and/or
             with slightly more prolonged or with slightly more vigorous activity than usual. Class
             II CHF or greater includes CHF resulting in mild symptoms with ordinary physical
             activity, or marked or severe limitations of activity [See Appendix B for New York
             Heart Association Functional Classification of Angina and CHF].

          -  Has known cardiac conduction defects that may predispose the patient to arrhythmias
             such as WPW; or a history of bradyarrhythmias, such as second or third degree heart
             block or sick sinus syndrome and no pacemaker

          -  Has 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).

          -  Is currently being treated with didanosine (ddI) or azathioprine. DdI and azathioprine
             must be discontinued before starting IV ribavirin
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

, 301-619-8447, [email protected]



Administrative Informations


NCT ID

NCT04283513

Organization ID

S-16-01


Responsible Party

Sponsor

Study Sponsor

U.S. Army Medical Research and Development Command


Study Sponsor

, , 


Verification Date

February 2021