Efficacy of Methylprednisolone for Hantavirus Cardiopulmonary Syndrome - Full Text View

Sponsor:	University of New Mexico
Collaborator:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	University of New Mexico
ClinicalTrials.gov Identifier:	NCT00128180

Purpose

The purpose of this study is to see if a drug, called methylprednisolone, is safe and effective in people with Hantavirus infection. Individuals 2 years of age or older are invited to participate in this study if their doctor suspects or knows they have Hantavirus infection. Volunteers will either be given methylprednisolone or placebo (contains no medication) through a needle inserted in a vein for 3 days. During the first 7 days of hospitalization procedures may include blood tests, physical exams, chest x-rays, and urine tests. During study visits on days 14, 28, 84 and 180 after diagnosis, the doctors will ask about health, examine the body, take a chest X-ray, collect blood for safety testing and for measuring antibodies, and do breathing tests on volunteers. Participants will be involved in the study for about 6 months.

Condition	Intervention	Phase
Hantavirus Infections	Drug: Methylprednisolone Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase II Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Methylprednisolone as a Treatment for Presumed Hantavirus Cardiopulmonary Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Hantavirus Infections

Drug Information available for: Prednisolone Prednisolone acetate Depo-medrol Medrol veriderm Methylprednisolone Prednisolone sodium phosphate Prednisolone Sodium Succinate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate 6-Methylprednisolone

U.S. FDA Resources

Further study details as provided by University of New Mexico:

Primary Outcome Measures:

The proportion of subjects who develop death, PaO2/FiO2 ratio less than or equal to 55, cardiac index less than or equal to 2.2, pulseless electrical activity, ventricular tachycardia or fibrillation [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Number of SAEs [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

ECMO [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Duration of ICU stays [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Duration of hospital stay [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Duration of shock and/or pressor/inotropic support [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Intubated and placed on a ventilator [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Refractory shock despite fluid resuscitation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Length of time on a ventilator [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Serum creatinine greater than or equal to 3.0 mg/dL [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	January 2003
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active: Active Comparator Active drug	Drug: Methylprednisolone Intravenous methylprednisolone 16 mg/kg/day for 3 days as follows: 8 mg/kg (up to 500 mg) given over first hour followed by 8 mg/kg over the next 23 hours; then 16 mg/kg (up to 1000 mg) on days 2 and 3 administered over 24 hours.
Placebo: Placebo Comparator Placebo	Drug: Placebo Placebo

Detailed Description:

This study is a phase II, randomized, double-blind, placebo-controlled evaluation of intravenous methylprednisolone versus placebo in treatment of Hantavirus cardiopulmonary syndrome (HCPS). Patients with suspected or known Hantavirus will be randomized to receive intravenous methylprednisolone or placebo over 3 days. Following the completion of this acute phase therapy, patients will be seen for follow up visits on days 14, 28, 84 and 6 months after study entry. Follow up visits will include a physical examination, including vital signs. In addition, blood will be drawn for a blood count, clinical chemistries, and quantitative polymerase chain reaction (day 14). Since Hantavirus pathogenesis involves the pulmonary system, other tests to be performed include chest x ray (day 28) and spirometry (days 28 and 180). The study will require 60 subjects with confirmed Hantavirus infection. Study subjects will include males and females greater than or equal to 2 years of age suspected of having Hantavirus disease. The enrolling co investigator must feel that Hantavirus disease is likely on the basis of the clinical syndrome. The primary study objectives are to: assess the efficacy of intravenous methylprednisolone in reducing the severity of HCPS and assess the safety of methylprednisolone in persons with suspected and proven Hantavirus infection. The secondary objectives are to: assess the impact of therapy on viremia and assess whether measurement of neutralizing antibody titers at entry or Human Leukocyte Antigen (HLA) typing can identify subgroups with increased risk of severe disease and/or death and whether therapy is effective in these subgroups. The primary endpoints will include: the proportion of subjects who develop one or more of the following critical events associated with severe disease 28 days after study entry: death, PaO2/FiO2 ratio less than or equal to 55, cardiac index less than or equal to 2.2, pulseless electrical activity, ventricular tachycardia or fibrillation; and number of serious adverse events determined by study investigators to be at least possibly related to study treatment. For this endpoint researchers will report: the median number of serious adverse events and the proportion that experience one or more serious adverse events. The secondary study endpoints include: to assist in defining the natural history of the disease but will not meaningfully affect treatment: Extracorporeal Membrane Oxygenation; duration of intensive care unit stays; duration of hospital stays; duration of shock and/or pressor/inotropic support; length of time on mechanical ventilation; intubated and placed on a ventilator; refractory shock despite fluid resuscitation; and serum creatinine greater than or equal to 3.0 milligrams/deciliter.

Eligibility

Ages Eligible for Study:	2 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Informed consent is given by patient or guardian.

And one of the following:

Confirmed diagnosis: Positive hantavirus IgM assay or detection of hantavirus in plasma or serum by RT-PCR in the presence of an acute febrile illness of less than 12 days duration, and
1. Onset of hypoxia (oxygen saturation less than or equal to 92% or requiring supplemental oxygen) one or more days after onset of symptoms, and
2. Development of pulmonary infiltrates on chest X-ray. OR
Presumptive diagnosis: The presumptive diagnosis of acute hantavirus disease of less than 12 days duration with:
1. Febrile illness (subjective or documented) in the judgment of the enrolling investigator; and
2. Headache or myalgia or at least one digestive symptom (nausea, diarrhea, vomiting, abdominal pain) and
3. A platelet count less than 150,000 on peripheral smear; and
4. Onset of hypoxia (oxygen saturation less than or equal to 92% or requiring supplemental oxygen) one or more days after onset of symptoms, and
5. Development of bilateral pulmonary infiltrates on chest X-ray

Exclusion Criteria:

Age less than 2 years.
If presumptive diagnosis is the inclusion criteria: subjects with a likely diagnosis other than hantavirus infection, including any positive culture or direct test for respiratory viruses (e.g., influenza, RSV, etc) or group A Streptococcus in a person with an illness compatible with streptococcal pharyngitis, a positive culture from a normally sterile site, or a presentation consistent with bacterial pneumonia.
Immunocompromised patients at risk of opportunistic infection (e.g., patients with HIV infection, underlying malignancy, or who have received chemotherapy or immunosuppressive drugs within 30 days.)
Patients who have or will receive any systemic antiviral medication (other than acyclovir, famciclovir, amantadine or rimantadine), systemic corticosteroids equivalent to approximately 0.5mg/kg prednisone, or any investigational drug within 30 days before enrollment or during treatment.
Any period of extreme bradycardia, pulseless electric activity
Active GI bleeding, with hematemesis, melena or hematochezia or documented by upper or lower endoscopy or by gastric aspiration.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00128180

Contacts

Contact: Gregory J Mertz

(505) 272-5666

gmertz@salud.unm.edu

Locations

Chile
Facultad de Medicina Clinica Alemana- Universidad del Desarrollo	Recruiting
Santiago, Chile

Sponsors and Collaborators

University of New Mexico

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:

Pablo Vial, MD

Universidad del Desarrollo

More Information

No publications provided

Responsible Party:	University of New Mexico ( Gregory J Mertz )
Study ID Numbers:	01-010
Study First Received:	August 5, 2005
Last Updated:	September 23, 2008
ClinicalTrials.gov Identifier:	NCT00128180 History of Changes
Health Authority:	Chile: Instituto de Salud Publica de Chile

Keywords provided by University of New Mexico:

hantaviruses, methylprednisolone, cardiopulmonary syndrome

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antineoplastic Agents
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Prednisolone acetate
Hantavirus Infections
Infection
Hormones
Neuroprotective Agents
Bunyaviridae Infections
Pathologic Processes
Syndrome
Therapeutic Uses

Methylprednisolone Hemisuccinate
RNA Virus Infections
Disease
Antineoplastic Agents, Hormonal
Gastrointestinal Agents
Methylprednisolone acetate
Protective Agents
Glucocorticoids
Pharmacologic Actions
Virus Diseases
Autonomic Agents
Prednisolone
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 30, 2009