The Efficacy of Intravenous Immunoglobulin Therapy for Severe 2019-nCoV Infected Pneumonia

Study Overview
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Brief Summary
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In this single-center, randomized, open-label, controlled study, the investigators will evaluate the efficacy and safety of Intravenous Immunoglobulin (IVIG) in combination with standard care for severe 2019 novel coronavirus (2019-nCoV) pneumonia.

Detailed Description
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In December 2019, viral pneumonia caused by a novel beta-coronavirus (2019-nCoV) outbroke in Wuhan, China. Part of patients rapidly progress severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe 2019-nCoV pneumonia besides the supportive care. Intravenous immunoglobulin (IVIG) has been shown to improve the treatment effect and prognosis of severe infection over the past decades with its capacity of proving passive immunity and anti-inflammatory, immunomodulatory effect. We hypothesized that IVIG therapy would improve the prognosis of severe and critically ill patients with 2019-nCoV. This single-center, randomized, open-label, controlled trial will evaluate the efficacy and safety of IVIG therapy in patients with severe or critically ill 2019-nCoV respiratory disease.

Official Title
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A Randomized, Open-label, Controlled, Single-center Study to Evaluate the Efficacy of Intravenous Immunoglobulin Therapy in Patients With Severe 2019- nCoV Pneumonia

Conditions
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2019-nCoV

Intervention / Treatment
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* Drug: Intravenous Immunoglobulin
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult aged >=18years old; Laboratory (RT-PCR) confirmed 2019-nCoV infection in throat swab and/or sputum and/or lower respiratory tract samples; The interval between the onset of symptoms and randomized is within 7 days. The onset of symptoms is mainly based on fever. If there is no fever, cough or other related symptoms can be used; Meet any of the following criteria for severe or critical ill conditions: Respiratory rate >=30/min; or Rest SPO2<=90%; or PaO2/FiO2<=300mmHg; or Respiratory failure and needs mechanical ventilation; or Shock occurs; or Multiple organ failure and needs ICU monitoring; Sign the Informed Consent Form on a voluntary basis. Exclusion Criteria: Exist of other evidences that can explain pneumonia including but not limited to: influenza A virus, influenza B virus, bacterial pneumonia, fungal pneumonia, noninfectious causes, etc.; Allergy to Intravenous Immunoglobulin or its preparation components; Patients with selective IgA deficiency Women who are pregnant or breast-feeding; Researchers consider unsuitable.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IVIG therapy+ standard care<br> | Drug: Intravenous Immunoglobulin<br>* IVIG 0.5g/kg/d for 5 days<br>* Other names: Human Immunoglobulin (pH4) for Intravenous Injection;Other: Standard care<br>* Standard care<br>|
| Placebo Comparator: Standard care<br> | Other: Standard care<br>* Standard care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement based on the 7-point scale | A decline of 2 points on the 7-point scale from admission means better outcome. The 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death). | 28 days after randomization | 
| Lower Murray lung injury score | Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition. | 7 days after randomization | 
| Lower Murray lung injury score | Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition. | 14 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day mortality | Number of deaths during study follow-up | Measured from Day 0 through Day 28 | 
| Duration of mechanical ventilation | Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up. | Measured from Day 0 through Day 28 | 
| Duration of hospitalization | Days that a participant spent at the hospital. Multiple hospitalizations are summed up. | Measured from Day 0 through Day 28 | 
| Proportion of patients with negative RT-PCR results | Proportion of patients with negative RT-PCR results of virus in upper and/or lower respiratory tract samples. | 7 and 14 days after randomization | 
| Proportion of patients in each category of the 7-point scale | Proportion of patients in each category of the 7-point scale, the 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death). | 7,14 and 28 days after randomization | 
| Proportion of patients with normalized inflammation factors | Proportion of patients with different inflammation factors in normalization range. | 7 and 14 days after randomization | 
| Frequency of Adverse Drug Events | Frequency of Adverse Drug Events | Measured from Day 0 through Day 28 | 
| Frequency of Serious Adverse Drug Events | Frequency of Serious Adverse Drug Events | Measured from Day 0 through Day 28 |