Washed Microbiota Transplantation for Patients With 2019-nCoV Infection

Study Overview
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Brief Summary
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Gut dysbiosis co-exists in patients with coronavirus pneumonia. Some of these patients would develop secondary bacterial infections and antibiotic-associated diarrhea (AAD). The recent study on using washed microbiota transplantation (WMT) as rescue therapy in critically ill patients with AAD demonstrated the important clinical benefits and safety of WMT. This clinical trial aims to evaluate the outcome of WMT combining with standard therapy for patients with 2019-novel coronavirus pneumonia, especially for those patients with dysbiosis-related conditions.

Detailed Description
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An ongoing outbreak of 2019 novel coronavirus was reported in Wuhan, China. 2019-nCoV has caused a cluster of pneumonia cases, and posed continuing epidemic threat to China and even global health. Unfortunately, there is currently no specific effective treatment for the viral infection and the related serious complications. It is in urgent need to find a new specific effective treatment for the 2019-nCoV infection. According to Declaration of Helsinki and International Ethical Guidelines for Health-related Research Involving Humans, the desperately ill patients with 2019-nCov infection during disease outbreaks have a moral right to try unvalidated medical interventions (UMIs) and that it is therefore unethical to restrict access to UMIs to the clinical trial context. There is a vital link between the intestinal tract and respiratory tract, which was exemplified by intestinal complications during respiratory disease and vice versa. Some of these patients can develop secondary bacterial infections and antibiotic-associated diarrhea (AAD). The recent study on using washed microbiota transplantation (WMT) as rescue therapy in critically ill patients with AAD demonstrated the important clinical benefits and safety of WMT. Additionally, the recent animal study provided direct evidence supporting that antibiotics could decrease gut microbiota and the lung stromal interferon signature and facilitate early influenza virus replication in lung epithelia. Importantly, the above antibiotics caused negative effects can be reversed by fecal microbiota transplantation (FMT) which suggested that FMT might be able to induce a significant improvement in the respiratory virus infection. Another evidence is that the microbiota could confer protection against certain virus infection such as influenza virus and respiratory syncytial virus by priming the immune response to viral evasion. The above results suggested that FMT might be a new therapeutic option for the treatment of virus-related pneumonia. The methodology of FMT recently was coined as WMT, which is dependent on the automatic facilities and washing process in a laboratory room. Patients underwent WMT with the decreased rate of adverse events and unchanged clinical efficacy in ulcerative colitis and Crohn's disease. This clinical trial aims to evaluate the outcome of WMT combining with standard therapy for patients with novel coronavirus pneumonia, especially for those patients with dysbiosis-related conditions.

Official Title
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Washed Microbiota Transplantation for Patients With 2019-nCoV Infection: a Randomized, Double-blind, Placebo-controlled Study

Conditions
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COVID-19 Complicated With Refractory Intestinal Infections

Intervention / Treatment
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* Other: washed microbiota transplantation
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 14-70 years old 2019 novel coronavirus pneumonia (severe type) Subjects voluntarily participate in the clinical trial and sign the informed consent Exclusion Criteria: Disturbance of consciousness Difficulty swallowing and frequent vomiting Patients requiring blood transfusion Pulmonary abscess, hepatitis, cirrhosis, tuberculosis, emphysema and pulmonary infarction Fungal and other identified pathogens infection Heart failure existed before diagnosis of novel coronavirus infection Liver function: alanine aminotransferase > 500 U/L Patients requiring hemodialysis Taking anticoagulant drugs due to cardiovascular and cerebrovascular diseases Other conditions that the investigator considers ineligible for clinical trial

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Observational group<br>5u washed microbiota suspension administered via nasogastric tube, nasojejunal tube or oral, combining with standard therapy. | Other: washed microbiota transplantation<br>* Washed microbiota suspension (5u) delivered through nasogastric tube, nasojejunal tube or oral. Dose and frequency: 5u, once.<br>* Other names: fecal microbiota transplantation;|
| Placebo Comparator: Control group<br>5 u placebo (edible suspension of the same color as the washed microbiota suspension) administered via nasogastric tube, nasojejunal tube or oral, combining with standard therapy. | Other: placebo<br>* Placebo (edible suspension of the same color as the washed microbiota suspension，5u) administered via nasogastric tube, nasojejunal tube or oral, combining with standard therapy. Dose and frequency: 5u, once.<br>* Other names: edible suspension;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with improvement from severe type to common type | Common type: Fever, respiratory tract and other symptoms, imaging examination shows pneumonia; Severe type (meeting any of the following）: (1) Respiratory distress，respiratory rate ≥ 30 bmp; (2) Oxygen saturation ≤ 93%；(3)PaO2/FiO2 ≤ 300mmHg. Critically severe type (meeting any of the following）: (1) Respiratory failure requiring mechanical ventilation; (2) Shock; (3) Combining with other organ failures, requiring ICU monitoring and treatment. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2, 2019-nCoV, Fecal Microbiota Transplantation, Washed Microbiota Transplantation