Efficacy of Methylprednisolone for Hantavirus Cardiopulmonary Syndrome

Hantavirus Infections Clinical Trial

Official title:

A Phase II Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Methylprednisolone as a Treatment for Presumed Hantavirus Cardiopulmonary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00128180
• Other study ID #: 01-010
• Secondary ID: U19 A1045452
• Status: Completed
• Phase: Phase 2
• First received: August 5, 2005
• Last updated: December 5, 2014
• Start date: January 2003
• Est. completion date: October 2011

Study information

• Verified date: December 2014
• Source: University of New Mexico
• Contact: n/a
• Is FDA regulated: No
• Health authority: Chile: Instituto de Salud Pública de Chile
• Study type: Interventional

Clinical Trial Summary

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.

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 (ECMO); 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: October 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hantavirus Infections
• Hantavirus Pulmonary Syndrome

Intervention

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

Locations

Country	Name	City	State
Chile	Facultad de Medicina Clinica Alemana- Universidad del Desarrollo	Santiago

Sponsors (2)

Lead Sponsor	Collaborator
University of New Mexico	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Chile, 

References & Publications (1)

Vial PA, Valdivieso F, Ferres M, Riquelme R, Rioseco ML, Calvo M, Castillo C, Díaz R, Scholz L, Cuiza A, Belmar E, Hernandez C, Martinez J, Lee SJ, Mertz GJ; Hantavirus Study Group in Chile. High-dose intravenous methylprednisolone for hantavirus cardiopu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		28 days	No
Primary	Number of Participants With SAEs	The Number of participants with SAEs	6 months	Yes
Secondary	Number of Participants on Extracorporeal Membrane Oxygenation (ECMO)	number of participants	6 months	No
Secondary	Duration of ICU Stays		6 months	No
Secondary	Duration of Hospital Stay in Days	Days	6 months	No
Secondary	Duration of Shock and/or Pressor/Inotropic Support	Pressor/inotropic support refers to the use of adrenaline-like medications to maintain blood pressure and cardiac output.	6 months	No
Secondary	Number of Participants Intubated and Placed on a Ventilator After Study Entry.	Participants	6 months	No
Secondary	Number of Participants Who Developed Refractory Shock Despite Fluid Resuscitation After Study Entry	Refractory shock refers to shock that persists despite fluid resucitation. Fluid resusitation refers to administration of intravenous fluids to maintain blood pressure and cardiac output.	6 months	No
Secondary	Length of Time on a Ventilator		6 months	No
Secondary	Development of Serum Creatinine Greater Than or Equal to 3.0 mg/dL After Study Entry		6 months	No