H-IVIG Treatment for Severe H1N1 2009

This study has been completed.
Sponsor:
Collaborators:
Queen Mary Hospital, Hong Kong
Pamela Youde Nethersole Eastern Hospital
Ruttonjee Hospital, Hong Kong
United Christian Hospital
Queen Elizabeth Hospital, Hong Kong
Caritas Medical Centre, Hong Kong
HK Red Cross Blood Transfusion Service, Hong Kong
Research Fund for the Control of Infectious Diseases, Hong Kong
Information provided by (Responsible Party):
Dr Ivan FN Hung, The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01617317
First received: June 2, 2012
Last updated: June 7, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention
Novel 2009 Influenza A (H1N1) Infection
Drug: Hyperimmune intravenous immunoglobulin
Drug: Intravenous immunoglobulin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Hyperimmune Intravenous Immunoglobulin Treatment for Severe H1N1 2009 Infection

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • Mortality [ Time Frame: From date of randomization until the date of death from any cause during hospitalization, assessed up to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events [ Time Frame: From date of randomization until the date of first documented adverse events due to treatment, assessed up to 1 week ] [ Designated as safety issue: Yes ]
    To assess the safety of H-IVIG and IVIG treatment

  • ICU length of stay [ Time Frame: Participants will be followed for the duration of ICU stay, an expected average of 4 weeks ] [ Designated as safety issue: No ]
  • Hospital length of stay [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 12 weeks ] [ Designated as safety issue: No ]
  • Nasopharyngeal viral load [ Time Frame: One day before randomization and up to 5 days after treatment ] [ Designated as safety issue: No ]
    To assess the change in nasopharyngeal viral load one day before randomization and 5 days after treatment

  • Cytokine/ chemokine [ Time Frame: One day before randomization and up to 5 days after treatment ] [ Designated as safety issue: No ]
    To assess the change in cytokine/ chemokine response one day before randomization and 5 days after treatment


Enrollment: 34
Study Start Date: January 2010
Study Completion Date: May 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: H-IVIG

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617317

Locations
Hong Kong
The University of Hong Kong, Queen Mary Hospital
Hong Kong, Hong Kong
Sponsors and Collaborators
The University of Hong Kong
Queen Mary Hospital, Hong Kong
Pamela Youde Nethersole Eastern Hospital
Ruttonjee Hospital, Hong Kong
United Christian Hospital
Queen Elizabeth Hospital, Hong Kong
Caritas Medical Centre, Hong Kong
HK Red Cross Blood Transfusion Service, Hong Kong
Research Fund for the Control of Infectious Diseases, Hong Kong
Investigators
Principal Investigator: Ivan FN Hung, MD FRCP The University of Hong Kong
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Ivan FN Hung, Clinical Associate Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT01617317     History of Changes
Other Study ID Numbers: HKU-09-330
Study First Received: June 2, 2012
Last Updated: June 7, 2012
Health Authority: Hong Kong: Department of Health
Hong Kong: Ethics Committee

Keywords provided by The University of Hong Kong:
H1N1 2009
hyperimmune IVIG
mortality
length of stay
viral load
cytokine

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014