Hantavirus InfectionsPhase 2NCT00128180
Efficacy of Methylprednisolone for Hantavirus Cardiopulmonary Syndrome
A Phase 2 study testing Methylprednisolone in people with Hantavirus Infections, run by University of New Mexico at 1 site in Chile.
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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Hantavirus Infections
- What is being tested?
- Methylprednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteChile
- Study dates
- Jan 2003to Oct 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
Show all 11Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Chile1 site
Facultad de Medicina Clinica Alemana- Universidad del Desarrollo
Santiago
About this study
Official title: A Phase II Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Methylprednisolone as a Treatment for Presumed Hantavirus Cardiopulmonary Syndrome
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.
Read the 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 (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.
- Conditions
- Hantavirus Infections
- Being tested
- Methylprednisolone, Placebo
- Keywords
- hantaviruses, methylprednisolone, cardiopulmonary syndrome
- Medical subject headings
- Hantavirus Infections, Hantavirus Pulmonary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Medrol
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | Methylprednisolone Receives: Drug: Methylprednisolone |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days
Number of Participants With SAEs
The Number of participants with SAEs
Measured: 6 months
Secondary outcomes (8)
Number of Participants on Extracorporeal Membrane Oxygenation (ECMO)
number of participants
Measured: 6 months
Duration of ICU Stays
Measured: 6 months
Duration of Hospital Stay in Days
Days
Measured: 6 months
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.
Measured: 6 months
Number of Participants Intubated and Placed on a Ventilator After Study Entry.
Participants
Measured: 6 months
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.
Measured: 6 months
Length of Time on a Ventilator
Measured: 6 months
Development of Serum Creatinine Greater Than or Equal to 3.0 mg/dL After Study Entry
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2005 (estimated)
- Study startJan 2003
- Primary completionDec 2010
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hantavirus InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of New Mexico
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pablo Vial, MD, Principal investigator, Universidad del Desarrollo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00128180
- Sponsor's protocol ID
- 01-010
- Other IDs
- U19 A1045452
- Status last verified
- Dec 2014
- First submitted
- 5 Aug 2005
- Last updated
- 24 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23784924
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Methylprednisolone as a Treatment for Presumed Hantavirus Cardiopulmonary Syndrome
- ClinicalTrials.gov ID
- NCT00128180
- Acronym / sponsor ID
- 01-010
- Conditions
- Hantavirus Infections
- Keywords
- hantaviruses, methylprednisolone, cardiopulmonary syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- University of New MexicoUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Jan 2003
- Primary completion
- Dec 2010 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 9 Aug 2005 (estimated)
- Results
- Posted 10 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Drug: MethylprednisoloneMethylprednisolone |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Informed consent is given by patient or guardian.
- 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
- Presumptive diagnosis: The presumptive diagnosis of acute hantavirus disease of less than 12 days duration with:
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylprednisoloneAlso: MedrolIntravenous 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. | Drug | Active |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
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
Number of Participants With SAEs
Time frame: 6 months
The Number of participants with SAEs
8 secondary outcomes
Number of Participants on Extracorporeal Membrane Oxygenation (ECMO)
Time frame: 6 months
Duration of ICU Stays
Time frame: 6 months
Duration of Hospital Stay in Days
Time frame: 6 months
Duration of Shock and/or Pressor/Inotropic Support
Time frame: 6 months
Number of Participants Intubated and Placed on a Ventilator After Study Entry.
Time frame: 6 months
Number of Participants Who Developed Refractory Shock Despite Fluid Resuscitation After Study Entry
Time frame: 6 months
Length of Time on a Ventilator
Time frame: 6 months
Development of Serum Creatinine Greater Than or Equal to 3.0 mg/dL After Study Entry
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23784924Vial 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.
Related trials for Hantavirus Infections
Active, not recruitingObservational study
Natural History of Andes Virus Infection
Andes Hantavirus
RecruitingObservational study
Biomedical Signal Extraction From Symptom Descriptions: An Observational Registry Using the OpenGenome Platform
Signs and Symptoms, Fever
RecruitingObservational study
Risk Assessment of Community Spread of Multiple Endemic Infectious Diseases in a One Health Perspective
Dengue, Chikungunya
RecruitingObservational study
Hantavirus Registry - HantaReg
Hantavirus Infections, Hemorrhagic Fever With Renal Syndrome
Not yet recruitingObservational study
Characterising the Loss of Haemostasis in Haemorrhagic Fever With Renal Syndrome
Haemorrhagic Fever With Renal Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pablo Vial, MD principal investigator
Universidad del Desarrollo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylprednisolone in people with Hantavirus Infections, run by University of New Mexico at 1 site in Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00128180, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2014.