Efficacy of Methylprednisolone for Hantavirus Cardiopulmonary Syndrome

NCT00128180 | Completed Phase 2 Results DMC

• 2 other identifiers: 01-010U19 A1045452
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hantavirus Infections

Keywords

hantaviruses, methylprednisolone, cardiopulmonary syndrome

Outcome Measures

Primary Outcomes (2)

• 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

• Number of Participants With SAEs

  The Number of participants with SAEs

  6 months

Secondary Outcomes (8)

• Number of Participants on Extracorporeal Membrane Oxygenation (ECMO)

  6 months

• Duration of ICU Stays

  6 months

• Duration of Hospital Stay in Days

  6 months

• Duration of Shock and/or Pressor/Inotropic Support

  6 months

• Number of Participants Intubated and Placed on a Ventilator After Study Entry.

  6 months

Study Arms (2)

Active

ACTIVE COMPARATOR

Methylprednisolone

Drug: Methylprednisolone

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Methylprednisolone DRUG

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.

Also known as: Medrol

Active

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Onset of hypoxia (oxygen saturation less than or equal to 92% or requiring supplemental oxygen) one or more days after onset of symptoms, and
• 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:
• Febrile illness (subjective or documented) in the judgment of the enrolling investigator; and
• Headache or myalgia or at least one digestive symptom (nausea, diarrhea, vomiting, abdominal pain) and
• A platelet count less than 150,000 on peripheral smear; and
• Onset of hypoxia (oxygen saturation less than or equal to 92% or requiring supplemental oxygen) one or more days after onset of symptoms, and
• Development of bilateral pulmonary infiltrates on chest X-ray

You may not qualify if:

• Age less than 2 years.
• 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.

Sponsors & Collaborators

• University of New Mexico: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Facultad de Medicina Clinica Alemana- Universidad del Desarrollo

Santiago, Chile

Location

Related Publications (1)

• Vial PA, Valdivieso F, Ferres M, Riquelme R, Rioseco ML, Calvo M, Castillo C, Diaz 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 cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial. Clin Infect Dis. 2013 Oct;57(7):943-51. doi: 10.1093/cid/cit394. Epub 2013 Jun 19.

  PMID: 23784924 RESULT

MeSH Terms

Conditions

Hantavirus Infections; Hantavirus Pulmonary Syndrome

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Bunyaviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Insufficiency; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

While the study reached the target accrual of 60 confirmed cases, it was not powered to detect a difference in mortality. Higher disease severity in the placebo group at entry complicated both the efficacy and safety analyses.

Results Point of Contact

• Title: Gregory Mertz, MD
• Organization: UNewMexico

gmertz@salud.unm.edu

5059808601

Study Officials

• Pablo Vial, MD

  Universidad del Desarrollo

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2005
• First Posted: August 9, 2005
• Study Start: January 1, 2003
• Primary Completion: December 1, 2010
• Study Completion: October 1, 2011
• Last Updated: December 24, 2014
• Results First Posted: July 10, 2012

Record last verified: 2014-12

Locations

CL (1)