Efficacy and Safety of High-Titer Versus Low-Titer Anti-Influenza Immune Plasma for the Treatment of Severe Influenza A
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Influenza |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 10/21/2017 |
| Start Date: | November 19, 2015 |
| End Date: | November 29, 2019 |
A Randomized Double-Blind, Phase 3 Study Comparing the Efficacy and Safety of High-Titer Versus Low-Titer Anti-Influenza Immune Plasma for the Teatment of Severe Influenza A
Background:
Most people infected with the influenza virus have mild symptoms. But some get very sick and
even die. Antibodies in the part of the blood called plasma fight germs like influenza.
Researchers want to see if plasma with high levels of antibodies helps more than plasma with
low levels when transfused into people with influenza. They have plasma from people with high
levels of antibodies from being infected with influenza or getting the influenza vaccine.
They also have plasma with low or no antibodies.
Objective:
To see if plasma with high levels of antibodies works better than plasma with low levels to
treat influenza.
Eligibility:
People ages 2 weeks and older who are hospitalized for symptoms of influenza
Design:
Participants will be screened with medical history and blood and urine tests. They may have a
nasal wash test for influenza. For this, they get a saline rinse in one nostril. A plastic
tube inserted in the nostril collects fluid.
The study lasts 28 days.
Participants will get routine influenza care. This includes standard drugs and possible chest
x-rays.
On Day 1, participants will have:
Physical exam
Blood tests
Throat swab
2 doses of plasma with high antibodies or low antibodies by IV catheter (tube) in a vein.
On Days 3 and 7, participants will return to the clinic, if no longer hospitalized, for
1-hour visits. The visits include:
Medical exam
Blood tests
Throat swab
On Days 2, 14, and 28, participants will be evaluated either at the clinic or by phone. They
will talk about their symptoms.
Most people infected with the influenza virus have mild symptoms. But some get very sick and
even die. Antibodies in the part of the blood called plasma fight germs like influenza.
Researchers want to see if plasma with high levels of antibodies helps more than plasma with
low levels when transfused into people with influenza. They have plasma from people with high
levels of antibodies from being infected with influenza or getting the influenza vaccine.
They also have plasma with low or no antibodies.
Objective:
To see if plasma with high levels of antibodies works better than plasma with low levels to
treat influenza.
Eligibility:
People ages 2 weeks and older who are hospitalized for symptoms of influenza
Design:
Participants will be screened with medical history and blood and urine tests. They may have a
nasal wash test for influenza. For this, they get a saline rinse in one nostril. A plastic
tube inserted in the nostril collects fluid.
The study lasts 28 days.
Participants will get routine influenza care. This includes standard drugs and possible chest
x-rays.
On Day 1, participants will have:
Physical exam
Blood tests
Throat swab
2 doses of plasma with high antibodies or low antibodies by IV catheter (tube) in a vein.
On Days 3 and 7, participants will return to the clinic, if no longer hospitalized, for
1-hour visits. The visits include:
Medical exam
Blood tests
Throat swab
On Days 2, 14, and 28, participants will be evaluated either at the clinic or by phone. They
will talk about their symptoms.
Significant morbidity and mortality from influenza infections occur despite treatment with
current antivirals. This randomized, double-blinded, multicenter phase 3 trial will assess
the efficacy and safety of high-titer versus low-titer anti-influenza immune plasma in
addition to standard care antivirals for the treatment of severe influenza A. Hospitalized
subjects with severe influenza A will be eligible for study participation. Up to 40 sites in
the United States will participate in this protocol. Adults and children may participate.
There is no exclusion for pregnancy.
A total of 150 eligible subjects will be randomized in a 2:1 ratio to receive either
high-titer anti-influenza plasma or control (low-titer) plasma. All plasma is from male
donors to minimize the risk of TRALI.
Subjects will be assessed on Study Day 0 (baseline) and on Study Days 1, 2, 3, 7, 14, and 28.
For participants who are not hospitalized on Days 2, 14, and 28, contact with the participant
for the purpose of limited study data collection for those days may be performed by
telephone. Study visits on Days 1, 3, 7 must occur in person. All subjects will undergo a
series of efficacy, safety, and HAI assessments during the study. Blood samples will be
collected on Day 0, 1, 3, and 7. OP swabs for influenza PCR will be obtained on Days 0 and 3.
current antivirals. This randomized, double-blinded, multicenter phase 3 trial will assess
the efficacy and safety of high-titer versus low-titer anti-influenza immune plasma in
addition to standard care antivirals for the treatment of severe influenza A. Hospitalized
subjects with severe influenza A will be eligible for study participation. Up to 40 sites in
the United States will participate in this protocol. Adults and children may participate.
There is no exclusion for pregnancy.
A total of 150 eligible subjects will be randomized in a 2:1 ratio to receive either
high-titer anti-influenza plasma or control (low-titer) plasma. All plasma is from male
donors to minimize the risk of TRALI.
Subjects will be assessed on Study Day 0 (baseline) and on Study Days 1, 2, 3, 7, 14, and 28.
For participants who are not hospitalized on Days 2, 14, and 28, contact with the participant
for the purpose of limited study data collection for those days may be performed by
telephone. Study visits on Days 1, 3, 7 must occur in person. All subjects will undergo a
series of efficacy, safety, and HAI assessments during the study. Blood samples will be
collected on Day 0, 1, 3, and 7. OP swabs for influenza PCR will be obtained on Days 0 and 3.
- ELIGIBILITY CRITERIA:
INCLUSION CRITERIA FOR ENROLLMENT (SCREENING):
- Hospitalization due to signs and symptoms of influenza (decision for hospitalization
will be up to the individual treating clinician).
- Study plasma available on-site or available within 24 hours after randomization.
- Not previously screened nor randomized in this study.
- Willingness to have blood and respiratory samples obtained and stored.
- Willingness to return for all required study visits and participate in study follow
up.
INCLUSION CRITERIA FOR RANDOMIZATION:
- Locally determined positive test for influenza A (by PCR, other nucleic acid testing,
or by rapid Ag) from a specimen obtained less than or equal to 48 hours prior to
randomization.
- Onset of illness less than or equal to 6 days before randomization, defined as when
the subject first experienced at least one respiratory symptom or fever.
- Hospitalized due to influenza, with anticipated hospitalization for more than 24 hours
after randomization. Criteria for hospitalization will be up to the individual
treating clinician.
- NEW or PEW score greater than or equal to 3 within 12 hours prior to randomization.
- ABO-compatible plasma available on-site or available within 24 hours after
randomization.
EXCLUSION CRITERIA FOR RANDOMIZATION:
Subjects who meet any of the following criteria will be excluded from study participation:
- Strong clinical evidence in the judgment of the site investigator that the etiology of
illness is primarily bacterial super-infection in origin. Co-infection would be
allowed, as there may be benefit to resolving influenza illness faster.
Super-infection, where influenza illness occurred and is resolving, and new bacterial
illness causing deterioration should be excluded. (e.g., if the subject's respiratory
infection is thought unlikely to benefit from additional antiviral therapy, this
exclusion criteria would be met).
- Prior treatment with any anti-influenza investigational drug, anti-influenza
investigational IVIG, or anti-influenza investigational plasma therapy within 30 days
prior to screening. Other investigational drug therapies (non-influenza) and
administration of plasma and/or IVIG for non-influenza reasons are allowed.
- History of allergic reaction to blood or plasma products (as judged by the site
investigator).
- A pre-existing condition or use of a medication that, in the opinion of the site
investigator, may place the individual at a substantially increased risk of thrombosis
(e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically
significant monoclonal gammopathy). Prior IVIG use alone would not meet exclusion
criteria, but the investigator should consider the potential for a hyper-coagulable
state.
- Subjects who, in the judgment of the site investigator, will be unlikely to comply
with the requirements of this protocol, including being uncontactable following
discharge from hospital.
- Medical conditions for which receipt of 450-700 mL of intravenous fluid may be
dangerous to the subject (e.g., decompensated congestive heart failure).
- Women that are pregnant or actively breast feeding (NIH site).
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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