H-IVIG Treatment for Severe H1N1 2009

June 7, 2012 updated by: Dr Ivan FN Hung, The University of Hong Kong

Hyperimmune Intravenous Immunoglobulin Treatment for Severe H1N1 2009 Infection

Treatment with hyperimmune intravenous immunoglobulin (H-IVIG), derived from convalescent plasma from patients recovered from H1N1 2009 influenza A infection, for patients with severe H1N1 2009 infection will decrease mortality, reduce viral load, and shorten the length of stay in ICU and hospital.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Since the emergence of the novel swine origin influenza A virus (H1N1 2009) in Mexico in March 2009, the virus has led to a pandemic in over 170 countries, resulting in over 180 thousands microbiologically confirmed cases and over 18000 mortality. This strain represents a quadruple re-assortment of two swine strains, one human strain, and one avian strain of influenza. Although the H1N1 2009 is causing a mild disease and has a relatively low mortality rate currently in Hong Kong, severe cases have been reported.

Patients infected with severe H1N1 2009 have overwhelmed the intensive care services in these countries and the mortality has rose up to 6% in Argentina and Brazil, and 0.4% in Australia. This is very much higher than the 0.06% mortality rate of the seasonal flu. Furthermore, there were reports of H1N1 2009 oseltamivir resistance and zanamivir is difficult to be delivered to the consolidated lungs in the severe cases when such drug is most needed. In Hong Kong, vaccination for the H1N1 2009 was prioritised to the older people aged 65 or above with chronic illness, younger people with chronic illness and health care workers. The healthy adults aged 18 to 65, who are most at risk of developing severe H1N1 2009 was not covered by the vaccination program. Experience from 1918 H1N1 pandemic and single case report on the treatment for severe H5N1 infection (Zhou et al. 2007) showed that hyperimmune convalescent plasma is useful (Luke et al. 2006). Mice experiments also showed that antibody therapy is highly effective in the case of H5N1 infection (Heltzer ML et al. 2009, Writing Committee of the Second World Heath Organization, 2008). Therefore, convalescent plasma from patients recovered from H1N1 2009 infection can be harvested to prepare for hyperimmune intravenous immunoglobulin (H-IVIG) and the prepared H-IVIG can be assessed in a randomised controlled trial for treatment of patients with severe H1N1 2009 infection.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • The University of Hong Kong, Queen Mary Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • (fulfill all criteria): male or female patients 18 years or older
  • written informed consent by patient or next of kin (if patients too ill)

  • diagnosis of H1N1 2009 infection satisfying both clinical and laboratory criteria:

    1. Laboratory criteria: at least one RT-PCR positive for H1N1 2009 from one of the clinical specimens (NPA, ETA, blood, urine or stool).
    2. Clinical criteria: patients admitted to ICU with severe community acquired pneumonia as defined by a CURB-65 score of 3 or more
  • deterioration during treatment with optimal antiviral (oral or inhaler agents only) and typical and atypical antimicrobial coverage
  • required ICU and ventilatory support and within 7 days onset of symptoms.

Exclusion Criteria:

  • age below 18 years
  • known hypersensitivity to immune globulin or any components of the formulation
  • known IgA deficiency
  • acquire the H1N1 2009 infection from health care facility
  • moribund patients or refusal of informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intravenous immunoglobulin
Single intravenous infusion of 0.4g/kg of simple IVIG which contain no H1N1 2009 antibody (manufactured before 2009).
Drug: Intravenous immunoglobulin
Single intravenous infusion of 0.4g/kg of simple IVIG
Other Names:
  • IVIG
Experimental: Hyperimmune intravenous immunoglobulin
Single intravenous infusion of 0.4g/kg of H1N1 2009 H-IVIG fractionated from convalescent plasma (H1N1 2009 antibody titer was 1:320 by hemagglutination inhibition and neutralizing antibody assays)
Drug: Hyperimmune intravenous immunoglobulin
Single intravenous infusion of 0.4g/kg of H1N1 2009 H-IVIG
Other Names:
  • H-IVIG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Mortality
Time Frame: From date of randomization until the date of death from any cause during hospitalization, assessed up to 6 months
From date of randomization until the date of death from any cause during hospitalization, assessed up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: From date of randomization until the date of first documented adverse events due to treatment, assessed up to 1 week
To assess the safety of H-IVIG and IVIG treatment
From date of randomization until the date of first documented adverse events due to treatment, assessed up to 1 week
ICU length of stay
Time Frame: Participants will be followed for the duration of ICU stay, an expected average of 4 weeks
Participants will be followed for the duration of ICU stay, an expected average of 4 weeks
Hospital length of stay
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 12 weeks
Participants will be followed for the duration of hospital stay, an expected average of 12 weeks
Nasopharyngeal viral load
Time Frame: One day before randomization and up to 5 days after treatment
To assess the change in nasopharyngeal viral load one day before randomization and 5 days after treatment
One day before randomization and up to 5 days after treatment
Cytokine/ chemokine
Time Frame: One day before randomization and up to 5 days after treatment
To assess the change in cytokine/ chemokine response one day before randomization and 5 days after treatment
One day before randomization and up to 5 days after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Collaborators

Queen Elizabeth Hospital, Hong Kong
Queen Mary Hospital, Hong Kong
Pamela Youde Nethersole Eastern Hospital
Ruttonjee Hospital, Hong Kong
United Christian Hospital
Caritas Medical Centre, Hong Kong
HK Red Cross Blood Transfusion Service, Hong Kong
Research Fund for the Control of Infectious Diseases, Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

June 2, 2012

First Submitted That Met QC Criteria

June 7, 2012

First Posted (Estimate)

June 12, 2012

Study Record Updates

Last Update Posted (Estimate)

June 12, 2012

Last Update Submitted That Met QC Criteria

June 7, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HKU-09-330

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Novel 2009 Influenza A (H1N1) Infection

Clinical Trials on Intravenous immunoglobulin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bosnia & Herzegovina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe