Novel 2009 Influenza A (H1N1) InfectionNCT01617317
H-IVIG Treatment for Severe H1N1 2009
A study testing Hyperimmune intravenous immunoglobulin and Intravenous immunoglobulin in people with Novel 2009 Influenza A (H1N1) Infection, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Novel 2009 Influenza A (H1N1) Infection
- What is being tested?
- Hyperimmune intravenous immunoglobulin and Intravenous immunoglobulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteHong Kong
- Study dates
- Jan 2010to May 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- (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:
- Laboratory criteria: at least one RT-PCR positive for H1N1 2009 from one of the clinical specimens (NPA, ETA, blood, urine or stool).
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Novel 2009 Influenza A (H1N1) Infection
- Being tested
- Hyperimmune intravenous immunoglobulin, Intravenous immunoglobulin
- Keywords
- H1N1 2009, hyperimmune IVIG, mortality, length of stay, viral load, cytokine
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperimmune intravenous immunoglobulinDrug
Also called H-IVIG
Single intravenous infusion of 0.4g/kg of H1N1 2009 H-IVIG
Intravenous immunoglobulinDrug
Also called IVIG
Single intravenous infusion of 0.4g/kg of simple IVIG
| Study group | Role | What they receive |
|---|---|---|
| Intravenous immunoglobulin | Active comparator | Single intravenous infusion of 0.4g/kg of simple IVIG which contain no H1N1 2009 antibody (manufactured before 2009). Receives: Drug: Intravenous immunoglobulin |
| Hyperimmune intravenous immunoglobulin | Experimental | 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) Receives: Drug: Hyperimmune intravenous immunoglobulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Measured: From date of randomization until the date of death from any cause during hospitalization, assessed up to 6 months
Secondary outcomes (5)
Adverse events
To assess the safety of H-IVIG and IVIG treatment
Measured: From date of randomization until the date of first documented adverse events due to treatment, assessed up to 1 week
ICU length of stay
Measured: Participants will be followed for the duration of ICU stay, an expected average of 4 weeks
Hospital length of stay
Measured: Participants will be followed for the duration of hospital stay, an expected average of 12 weeks
Nasopharyngeal viral load
To assess the change in nasopharyngeal viral load one day before randomization and 5 days after treatment
Measured: One day before randomization and up to 5 days after treatment
Cytokine/ chemokine
To assess the change in cytokine/ chemokine response one day before randomization and 5 days after treatment
Measured: One day before randomization and up to 5 days after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2012 (estimated)
- Study startJan 2010
- Primary completionNov 2011
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Novel 2009 Influenza A (H1N1) InfectionStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Dr Ivan FN Hung, The University of Hong Kong
- Investigators
- Ivan FN Hung, MD FRCP, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01617317
- Sponsor's protocol ID
- HKU-09-330
- Status last verified
- Jun 2012
- First submitted
- 2 Jun 2012
- Last updated
- 12 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.
PubMed 21248066Hung IF, To KK, Lee CK, Lin CK, Chan JF, Tse H, Cheng VC, Chen H, Ho PL, Tse CW, Ng TK, Que TL, Chan KH, Yuen KY. Effect of clinical and virological parameters on the level of neutralizing antibody against pandemic influenza A virus H1N1 2009. Clin Infect Dis. 2010 Aug 1;51(3):274-9. doi: 10.1086/653940.
PubMed 20575664To KK, Hung IF, Li IW, Lee KL, Koo CK, Yan WW, Liu R, Ho KY, Chu KH, Watt CL, Luk WK, Lai KY, Chow FL, Mok T, Buckley T, Chan JF, Wong SS, Zheng B, Chen H, Lau CC, Tse H, Cheng VC, Chan KH, Yuen KY. Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis. 2010 Mar 15;50(6):850-9. doi: 10.1086/650581.
PubMed 20136415Wu JT, Lee CK, Cowling BJ, Yuen KY. Logistical feasibility and potential benefits of a population-wide passive-immunotherapy program during an influenza pandemic. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3269-74. doi: 10.1073/pnas.0911596107. Epub 2010 Feb 1.
PubMed 20133660Wong HK, Lee CK, Hung IF, Leung JN, Hong J, Yuen KY, Lin CK. Practical limitations of convalescent plasma collection: a case scenario in pandemic preparation for influenza A (H1N1) infection. Transfusion. 2010 Sep;50(9):1967-71. doi: 10.1111/j.1537-2995.2010.02651.x.
PubMed 20412524Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med. 2007 Oct 4;357(14):1450-1. doi: 10.1056/NEJMc070359. No abstract available.
PubMed 17914053Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006 Oct 17;145(8):599-609. doi: 10.7326/0003-4819-145-8-200610170-00139. Epub 2006 Aug 29.
PubMed 16940336Hung IFN, To KKW, Lee CK, Lee KL, Yan WW, Chan K, Chan WM, Ngai CW, Law KI, Chow FL, Liu R, Lai KY, Lau CCY, Liu SH, Chan KH, Lin CK, Yuen KY. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013 Aug;144(2):464-473. doi: 10.1378/chest.12-2907.
PubMed 23450336
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperimmune Intravenous Immunoglobulin Treatment for Severe H1N1 2009 Infection
- ClinicalTrials.gov ID
- NCT01617317
- Acronym / sponsor ID
- HKU-09-330
- Conditions
- Novel 2009 Influenza A (H1N1) Infection
- Keywords
- H1N1 2009, hyperimmune IVIG, mortality, length of stay, viral load, cytokine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- 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
- Study start
- Jan 2010
- Primary completion
- Nov 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 12 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous immunoglobulin | Active comparator | Drug: Intravenous immunoglobulinSingle intravenous infusion of 0.4g/kg of simple IVIG which contain no H1N1 2009 antibody (manufactured before 2009). |
| Hyperimmune intravenous immunoglobulin | Experimental | Drug: Hyperimmune intravenous immunoglobulinSingle 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- (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:
- 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.
Key exclusion criteria (5 listed)
- 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.
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 |
|---|---|---|
| Hyperimmune intravenous immunoglobulinAlso: H-IVIGSingle intravenous infusion of 0.4g/kg of H1N1 2009 H-IVIG | Drug | Hyperimmune intravenous immunoglobulin |
| Intravenous immunoglobulinAlso: IVIGSingle intravenous infusion of 0.4g/kg of simple IVIG | Drug | Intravenous immunoglobulin |
Primary outcome
Mortality
Time frame: From date of randomization until the date of death from any cause during hospitalization, assessed up to 6 months
5 secondary outcomes
Adverse events
Time frame: 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
Hospital length of stay
Time frame: 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
Cytokine/ chemokine
Time frame: One day before randomization and up to 5 days after treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2012.
- Background: PubMed 21248066Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.
- Background: PubMed 20575664Hung IF, To KK, Lee CK, Lin CK, Chan JF, Tse H, Cheng VC, Chen H, Ho PL, Tse CW, Ng TK, Que TL, Chan KH, Yuen KY. Effect of clinical and virological parameters on the level of neutralizing antibody against pandemic influenza A virus H1N1 2009. Clin Infect Dis. 2010 Aug 1;51(3):274-9. doi: 10.1086/653940.
- Background: PubMed 20136415To KK, Hung IF, Li IW, Lee KL, Koo CK, Yan WW, Liu R, Ho KY, Chu KH, Watt CL, Luk WK, Lai KY, Chow FL, Mok T, Buckley T, Chan JF, Wong SS, Zheng B, Chen H, Lau CC, Tse H, Cheng VC, Chan KH, Yuen KY. Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis. 2010 Mar 15;50(6):850-9. doi: 10.1086/650581.
- Background: PubMed 20133660Wu JT, Lee CK, Cowling BJ, Yuen KY. Logistical feasibility and potential benefits of a population-wide passive-immunotherapy program during an influenza pandemic. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3269-74. doi: 10.1073/pnas.0911596107. Epub 2010 Feb 1.
- Background: PubMed 20412524Wong HK, Lee CK, Hung IF, Leung JN, Hong J, Yuen KY, Lin CK. Practical limitations of convalescent plasma collection: a case scenario in pandemic preparation for influenza A (H1N1) infection. Transfusion. 2010 Sep;50(9):1967-71. doi: 10.1111/j.1537-2995.2010.02651.x.
- Background: PubMed 17914053Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med. 2007 Oct 4;357(14):1450-1. doi: 10.1056/NEJMc070359. No abstract available.
- Background: PubMed 16940336Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006 Oct 17;145(8):599-609. doi: 10.7326/0003-4819-145-8-200610170-00139. Epub 2006 Aug 29.
- Derived from this study: PubMed 23450336Hung IFN, To KKW, Lee CK, Lee KL, Yan WW, Chan K, Chan WM, Ngai CW, Law KI, Chow FL, Liu R, Lai KY, Lau CCY, Liu SH, Chan KH, Lin CK, Yuen KY. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013 Aug;144(2):464-473. doi: 10.1378/chest.12-2907.
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.
Ivan FN Hung, MD FRCP principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hyperimmune intravenous immunoglobulin and Intravenous immunoglobulin in people with Novel 2009 Influenza A (H1N1) Infection, run by The University of Hong Kong at 1 site in Hong Kong.
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 7 inclusion and 5 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 12 Jun 2012. 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 Hong Kong. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Mortality (time frame: From date of randomization until the date of death from any cause during hospitalization, assessed up to 6 months). 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 NCT01617317, which also lists 8 linked publications.
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 12 Jun 2012.