Treatment of Viral Hemorrhagic Fevers With Intravenous Ribavirin in Military Treatment Facilities

NCT00992693 | Withdrawn Phase 2

• 1 other identifier: C2009.140
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2 study of the safety and efficacy of Intravenous (IV) Ribavirin in treating patients presenting with a probable or suspected case of viral hemorrhagic fever (either Crimean Congo or Lassa Fever) at a military medical treatment hospital. All patients will be treated with a 10 day course of IV Ribavirin if they meet all the inclusion and none of the exclusion criteria.

Conditions

Crimean-Congo Hemorrhagic Fever; Lassa Fever

Keywords

Crimean-Congo Hemorrhagic Fever; Lassa Fever; CCHF; LF; Viral Hemorrhagic Fever; VHF; Ribavirin

Outcome Measures

Primary Outcomes (2)

• Number of adverse events

  5 years

• Number of deaths of individuals with viral hemorrhagic fever (Crimean-Congo hemorrhagic fever or Lassa fever) who received at least four doses of IV Ribavirin

  5 years

Secondary Outcomes (1)

• Number of clinical events

  5 years

Study Arms (1)

Treatment with IV Ribavirin

EXPERIMENTAL

In this open label treatment study, the investigators intend to treat all subjects who present with a tentative diagnosis of VHF and meet entry criteria with a 10 day course of IV Ribavirin.

Drug: Ribavirin (Virazole) Injection

Interventions

Ribavirin (Virazole) Injection DRUG

The drug is to be administered in a volume of 50-100 ml of normal saline to be infused over 30-40 minutes. 1\) Loading dose: 33 mg/kg (maximum dose 2.64 g)(1 dose) 2) Followed by a dose of 16 mg/kg (max dose 1.28 g) every 6 hours for the first 4 days (15 doses) 3) Followed by a dose of 8 mg/kg (maximum dose 0.64 g) every 8 hours for the subsequent 6 days (18 doses) Ten day course of treatment with follow up between day 28 to day 60.

Also known as: Virazole Injection, 100 mg/ml

Treatment with IV 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:

• An individual will be enrolled in this study if the patient:
• Meets the case definition for a probable or a suspected case of CCHF or LF (see below).
• 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 Events, Serious and Unexpected Adverse Events for the duration of the study.
• Agrees to a follow-up visit and to donate blood and urine specimens at day 14 (±2 days) 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.
• Woman of childbearing age must have a pregnancy test performed. If negative, she must agree not to become pregnant during treatment and for 7 months after receiving Ribavirin. She also must agree to not breast feed during treatment and for 7 months after receiving Ribavirin. Two reliable forms of effective contraception must be used including one barrier method during treatment and during the 7 month post-treatment period. She will be counseled concerning the risks of IV Ribavirin versus no treatment if the pregnancy test is positive.
• Man agrees not to have intercourse with pregnant woman 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. At least two reliable forms of effective contraception must be used including one barrier method during treatment and during the 7 month post-treatment period to avoid a pregnancy.
• Has a hemoglobin greater than or equal to10 g/dL before starting IV Ribavirin
• Note: Malaria should be excluded as a possibility for illness in patients suspected to have VHF.
• Probable Case of Crimean-Congo Hemorrhagic Fever:
• All subjects will have a history of possible exposure to CCHF, either having:
• Worked or slept outdoors in the CCHF endemic area within 2 weeks of illness onset, with or without a history of tick-bite or tick exposure, (Endemic area includes, but not necessarily limited to: Saudi Arabia, Kuwait, Oman, United Arab Emirates, Iran, Iraq, Turkey, Greece, Bulgaria, Albania, Montenegro, the Kosovo region of Serbia, Bosnia-Herzegovina, Macedonia, the whole of Africa, India, Pakistan, Afghanistan, Kazakhstan, Uzbekistan, Kyrgyzstan, Tajikistan, Turkmenistan, Azerbaijan, Georgia, the Crimean region of the Ukraine, Rostov-Don and Astrakhan regions of Russia, and the Xinjiang \[northwestern\] region of the People's Republic of China), OR

You may not qualify if:

• Has known intolerance to Ribavirin.
• 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 hemoglobin less than 10 g/dL that cannot be corrected to 10 g/dL before initiation of IV Ribavirin
• Has history of hemoglobinopathies (i.e., sickle-cell anemia or thalassemia major).
• Has history of autoimmune hepatitis.
• Has a calculated serum creatinine clearance of \< 30 mL/min.
• History of such as second or third degree heart block or sick sinus syndrome and without a pacemaker and no capability of a pacemaker placement or Wolfe-Parkinson-White Syndrome.
• A sinus bradycardia of less than 40 beats per minute.
• Is currently being treated with Didanosine (ddI). ddI must be discontinued before starting IV Ribavirin.
• At the principal investigator's (PI) discretion, an individual may be treated with IV Ribavirin, with caution, if one of these criteria is present:
• A positive pregnancy test. The individual will be informed of the risk and benefit of treatment with IV Ribavirin versus no treatment with IV Ribavirin in CCHF (generally associated with high mortality) and severe cases of Lassa fever with high mortality rates versus mild cases of Lassa fever with low mortality rates.
• A New York Heart Association Cardiac functional capacity of Class II or greater for ASHD and CHF.
• Known cardiac defects that my predispose the subject to bradyarrhythmias, such as second or third degree heart block or sick sinus syndrome without a pacemaker, but capability of pacemaker placement, if needed.
• Sinus bradycardia of 41-49 beats per minutes if the individual is not known to have a low resting heart rate related to physical conditioning.
• Use of drugs known to result in bradyarrhythmias (certain betablockers and calcium channel blockers, digoxin).

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (1)

Landstuhl Regional Medical Center

Landstuhl, Rhineland-Palatinate, Germany

Location

MeSH Terms

Conditions

Hemorrhagic Fever, Crimean; Lassa Fever; Hemorrhagic Fevers, Viral

Interventions

Ribavirin; Injections

Condition Hierarchy (Ancestors)

Arbovirus Infections; Vector Borne Diseases; Infections; Tick-Borne Diseases; Virus Diseases; Bunyaviridae Infections; RNA Virus Infections; Arenaviridae Infections

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Elizabeth Rini, MD

  Landstuhl Regional Medical Center, Germany

  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: October 8, 2009
• First Posted: October 9, 2009
• Study Start: September 1, 2009
• Primary Completion: July 19, 2016
• Study Completion: December 17, 2019
• Last Updated: January 2, 2020

Record last verified: 2019-09

Locations

DE (1)