Back to resultsEvaluating the Impact of EnteraGam In People With COVID-19 (PICNIC)
Primary Purpose
Covid19
Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Bovine Plasma-Derived Immunoglobulin Concentrate
Standard of care
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring SARS-CoV-2, Coronavirus, Bovine Plasma-Derived Immunoglobulin
Eligibility Criteria
Inclusion Criteria:
- Subject is ≥18 years of age.
- Male or female. Females of childbearing (reproductive) potential must have a negative urine pregnancy test at screening.
Subject with diagnosis of COVID-19 based on + RNA or immunoglobulin M (IgM) test or compatible clinical presentation* who:
- is being discharged from the emergency department without hospitalization, or
- is admitted to the hospital or was previously hospitalized and still in the hospital, does not require invasive mechanical ventilation and does not require management in the intensive care unit. Inpatients can be enrolled in the study at any time of their hospitalization, if they comply with the inclusion criteria.
(*)Compatible clinical presentation will consider compatible symptoms (cough, fever, myalgia, dyspnea, ageusia / anosmia) and examination of general condition, heart rate and respiratory rate, oxygen saturation, cardiopulmonary auscultation, compatible radiology.
- Ability to consume EnteraGam.
- Subject or surrogate decision maker is capable of understanding the requirements of the study, understands the language of the informed consent form, and is capable and willing to sign the informed consent form.
Exclusion Criteria:
- Female subjects who are pregnant or breast-feeding.
- Subject is enrolled in another randomized clinical trial.
- Subject is taking anti-IL-6 treatment (e.g. tocilizumab), anti-IL-1 treatment (e.g. canakinumab, anakinra), or other biologic immunomodulators or immunosuppressant drugs. Note: Topical/inhaled immunomodulators and corticosteroids are not restricted.
- Subject has immediate need for GI surgery or intervention for active GI bleeding, pancreatitis, peritonitis, intestinal obstruction, or intra-abdominal abscess.
- Subject has active inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, or celiac disease), GI malignancy, GI obstruction, pancreatitis, gastroparesis, carcinoid syndrome, amyloidosis, ileus, or cholelithiasis.
- Subject has active gastric ulcer, duodenal ulcer, diverticulitis, colitis, enteritis, infectious gastroenteritis, or GI neoplasm, other than benign polyps.
- Subject has a history of allergy or intolerance to beef or to any ingredient in the product.
- Subject has active drug or alcohol abuse that in the opinion of the investigator may interfere with the subject's ability to comply with this protocol.
- History of uncontrolled psychiatric disorders (includes significant depression or suicidal ideation), that in the opinion of the investigator may interfere with the subject's ability to comply with this protocol.
- In the opinion of the investigator, progression to death is imminent and highly likely within the next 24 hours.
Sites / Locations
- Hospital del Mar
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
EnteraGam + standard of care
Control (standard of care)
Arm Description
Subjects will receive EnteraGam® (oral nutritional therapy) + standard of care for COVID-19 for 2 weeks. Total study duration (including the screening phase) will be approximately 4 weeks.
Subjects will receive standard of care for COVID-19 alone for 2 weeks. Total study duration (including the screening phase) will be approximately 4 weeks.
Outcomes
Primary Outcome Measures
Change in plasma IL-6 levels
Variation of IL-6 levels measured in plasma
COVID-19 disease progression by Week 2
Percentage of patients with COVID-19 who have disease progression by Week 2, defined as:
For outpatients, return to emergency department for COVID-19 related manifestations or worsening of ≥1 level on the World Health Organization (WHO) 9-point ordinal scale.
For inpatients, worsening of ≥1 level on the WHO 9-point ordinal scale.
Secondary Outcome Measures
Change in dyspnea
Variation of dyspnea presentation at Week 2 compared to baseline, assessed by daily symptoms questionnaire
Change in diarrhea
Variation of diarrhea presentation at Week 2 compared to baseline, assessed by daily symptoms questionnaire
Change in fever
Variation of fever presentation at Week 2 compared to baseline
Change in neutrophil count
Variation of neutrophil count at Week 2 compared to baseline
Change in lymphocyte count
Variation of lymphocyte count at Week 2 compared to baseline
Change in neutrophil/lymphocyte ratio
Variation of neutrophil/lymphocyte ratio at Week 2 compared to baseline
Change in platelet count
Variation of platelet count at Week 2 compared to baseline
Change in C-reactive protein
Variation of C-reactive protein levels at Week 2 compared to baseline
Change in ferritin
Variation of ferritin levels at Week 2 compared to baseline
Change in D-dimer
Variation of D-dimer levels at Week 2 compared to baseline
Change in AST
Variation of Aspartate Transaminase (AST/GOT) levels at Week 2 compared to baseline
Change in ALT
Variation of Alanine Transaminase (ALT/GPT) levels at Week 2 compared to baseline
Time to worsening clinical status
Time elapsed between baseline and disease progression, defined as:
For outpatients, return to emergency department for COVID-19 related manifestations or worsening of ≥1 level on the WHO 9-point ordinal scale.
For inpatients, worsening of ≥1 level on the WHO 9-point ordinal scale.
Full Information
NCT ID
NCT04682041
First Posted
December 18, 2020
Last Updated
April 18, 2023
Sponsor
Entera Health, Inc
Collaborators
Lemus Buhils, SL, Clinical Research Unit, IMIM (Hospital del Mar Medical Research Institute)
1. Study Identification
Unique Protocol Identification Number
NCT04682041
Brief Title
Evaluating the Impact of EnteraGam In People With COVID-19
Acronym
PICNIC
Official Title
Randomized Open-Label Clinical Study Evaluating the Impact of EnteraGam, a Nutritional Intervention Containing Bovine Plasma-Derived Immunoglobulin CoNcentrate, on Clinical Outcomes In People With COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
December 22, 2020 (Actual)
Primary Completion Date
December 20, 2021 (Actual)
Study Completion Date
February 21, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Entera Health, Inc
Collaborators
Lemus Buhils, SL, Clinical Research Unit, IMIM (Hospital del Mar Medical Research Institute)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Background:
Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged as a potentially life-threatening disease in Wuhan, China, at the end of 2019. Since then, it has spread to almost 200 countries and infection rates are rapidly accelerating.
Overactivation of T cells resulting in immune dysfunction, dysfunction of the renin angiotensin system, and antibody-dependent enhancement are thought to contribute to the cytokine storm that results in acute respiratory distress syndrome (ARDS), culminating in death. In addition to causing respiratory symptoms, SARS-CoV-2 can cause diarrhea and has been isolated from the stool. SARS-CoV-2 binds to Angiotensin-converting enzyme 2 (ACE2) on lung alveolar type 2 cells, but ACE2 is also expressed in the absorptive enterocytes from the ileum and colon. The diarrhea may be caused by increased intestinal permeability due to binding of these receptors by the SARS-CoV-2.
Thus, an intervention to attenuate this cytokine storm may improve clinical outcomes in people with COVID-19. One such intervention is oral administration of serum bovine immunoglobulins, which decreases interleukin-6 (IL-6) levels safely with minimal side effects. Animal and human clinical studies have shown dietary supplementation with oral immunoglobulins improves mucosal immunity, specifically respiratory/pulmonary and GI mucosa, and decreases systemic inflammation, reducing the symptoms and severity of pulmonary inflammation and viral infections.
Hypothesis:
Dietary supplementation with EnteraGam® will decrease IL-6 levels and prevent disease progression in SARS-CoV-2 infected individuals.
Objectives:
To evaluate the effectiveness of the oral nutritional therapy EnteraGam® (serum-derived bovine immunoglobulin/protein isolate) to prevent disease progression of COVID-19 and to decrease IL-6 levels as compared to standard of care in subjects with COVID-19.
Methods:
Randomized open-label clinical study evaluating the effectiveness of EnteraGam® 10.0 g BID (every 12 hours) added to standard of care, as compared to standard of care alone, in subjects with COVID-19.
Detailed Description
Subject population:
Outpatient and inpatient male and non-pregnant females ≥18 years old, diagnosed with COVID-19 in the emergency department or admitted to the hospital but not requiring invasive mechanical ventilation or in the ICU.
Approximately 420 subjects will be randomized (2:1 ratio), 280 in the EnteraGam® arm and 140 in the control (standard of care) arm.
Nutritional intervention:
ImmunoLin is the active ingredient in EnteraGam®, a medical food developed and marketed by Entera Health in the US since 2013. ImmunoLin is an edible bovine plasma-derived immunoglobulin concentrate developed in 2001 as an immunoglobulin enriched plasma preparation for the human dietary supplement market. ImmunoLin is Generally Regarded as Safe (GRAS) following a letter of no objection from the US FDA in 2008. Physicians have prescribed EnteraGam® for patients with a variety of GI-related conditions.
Statistical methodology:
Efficacy: Based on per protocol analysis. Subjects lacking an assessment at Week 2 will be included in the analysis using the last available post-baseline data. Three pre-specified secondary analyses will be performed: 1) restricted to subjects with a comorbidity considered a major risk factor for hospitalization and disease severity (diabetes, cardiovascular disease, chronic lung disease, chronic renal disease, immunocompromised state); 2) restricted to age ≥ 50 years; 3) by inpatient only and outpatient only subgroups.
Additional analysis of covariance models with adjustment for Baseline characteristics and interactions may be examined in supportive or exploratory analyses.
Safety: All safety analyses will be based on all subjects who are randomized to EnteraGam and subsequently receive at least 1 packet of investigational product. Safety assessments will be analyzed by frequency of events/abnormalities for categorical values or summarized using descriptive statistics (mean, standard deviation, median, range, and number of observations).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
SARS-CoV-2, Coronavirus, Bovine Plasma-Derived Immunoglobulin
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized open-label clinical study evaluating the effectiveness of EnteraGam 10.0 g BID added to standard of care, as compared to standard of care alone, in subjects with COVID-19. Eligible subjects will be randomized in a 2:1 ratio.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EnteraGam + standard of care
Arm Type
Experimental
Arm Description
Subjects will receive EnteraGam® (oral nutritional therapy) + standard of care for COVID-19 for 2 weeks. Total study duration (including the screening phase) will be approximately 4 weeks.
Arm Title
Control (standard of care)
Arm Type
Other
Arm Description
Subjects will receive standard of care for COVID-19 alone for 2 weeks. Total study duration (including the screening phase) will be approximately 4 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Bovine Plasma-Derived Immunoglobulin Concentrate
Other Intervention Name(s)
EnteraGam®
Intervention Description
EnteraGam® 10.0 g, containing 5.0 g of serum-derived bovine immunoglobulin/protein isolate (SBI) BID (every 12 hours) for 2 weeks.
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
Standard of care PSMAR protocol for COVID-19 patients.
Primary Outcome Measure Information:
Title
Change in plasma IL-6 levels
Description
Variation of IL-6 levels measured in plasma
Time Frame
From baseline to Week 2
Title
COVID-19 disease progression by Week 2
Description
Percentage of patients with COVID-19 who have disease progression by Week 2, defined as:
For outpatients, return to emergency department for COVID-19 related manifestations or worsening of ≥1 level on the World Health Organization (WHO) 9-point ordinal scale.
For inpatients, worsening of ≥1 level on the WHO 9-point ordinal scale.
Time Frame
From baseline to Week 2
Secondary Outcome Measure Information:
Title
Change in dyspnea
Description
Variation of dyspnea presentation at Week 2 compared to baseline, assessed by daily symptoms questionnaire
Time Frame
At Week 2
Title
Change in diarrhea
Description
Variation of diarrhea presentation at Week 2 compared to baseline, assessed by daily symptoms questionnaire
Time Frame
At Week 2
Title
Change in fever
Description
Variation of fever presentation at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in neutrophil count
Description
Variation of neutrophil count at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in lymphocyte count
Description
Variation of lymphocyte count at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in neutrophil/lymphocyte ratio
Description
Variation of neutrophil/lymphocyte ratio at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in platelet count
Description
Variation of platelet count at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in C-reactive protein
Description
Variation of C-reactive protein levels at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in ferritin
Description
Variation of ferritin levels at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in D-dimer
Description
Variation of D-dimer levels at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in AST
Description
Variation of Aspartate Transaminase (AST/GOT) levels at Week 2 compared to baseline
Time Frame
At Week 2
Title
Change in ALT
Description
Variation of Alanine Transaminase (ALT/GPT) levels at Week 2 compared to baseline
Time Frame
At Week 2
Title
Time to worsening clinical status
Description
Time elapsed between baseline and disease progression, defined as:
For outpatients, return to emergency department for COVID-19 related manifestations or worsening of ≥1 level on the WHO 9-point ordinal scale.
For inpatients, worsening of ≥1 level on the WHO 9-point ordinal scale.
Time Frame
From baseline to Week 2
Other Pre-specified Outcome Measures:
Title
Incidence of Adverse Events
Description
Incidence of serious and non-serious adverse events.
Time Frame
From baseline to Week 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject is ≥18 years of age.
Male or female. Females of childbearing (reproductive) potential must have a negative urine pregnancy test at screening.
Subject with diagnosis of COVID-19 based on + RNA or immunoglobulin M (IgM) test or compatible clinical presentation* who:
is being discharged from the emergency department without hospitalization, or
is admitted to the hospital or was previously hospitalized and still in the hospital, does not require invasive mechanical ventilation and does not require management in the intensive care unit. Inpatients can be enrolled in the study at any time of their hospitalization, if they comply with the inclusion criteria.
(*)Compatible clinical presentation will consider compatible symptoms (cough, fever, myalgia, dyspnea, ageusia / anosmia) and examination of general condition, heart rate and respiratory rate, oxygen saturation, cardiopulmonary auscultation, compatible radiology.
Ability to consume EnteraGam.
Subject or surrogate decision maker is capable of understanding the requirements of the study, understands the language of the informed consent form, and is capable and willing to sign the informed consent form.
Exclusion Criteria:
Female subjects who are pregnant or breast-feeding.
Subject is enrolled in another randomized clinical trial.
Subject is taking anti-IL-6 treatment (e.g. tocilizumab), anti-IL-1 treatment (e.g. canakinumab, anakinra), or other biologic immunomodulators or immunosuppressant drugs. Note: Topical/inhaled immunomodulators and corticosteroids are not restricted.
Subject has immediate need for GI surgery or intervention for active GI bleeding, pancreatitis, peritonitis, intestinal obstruction, or intra-abdominal abscess.
Subject has active inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, or celiac disease), GI malignancy, GI obstruction, pancreatitis, gastroparesis, carcinoid syndrome, amyloidosis, ileus, or cholelithiasis.
Subject has active gastric ulcer, duodenal ulcer, diverticulitis, colitis, enteritis, infectious gastroenteritis, or GI neoplasm, other than benign polyps.
Subject has a history of allergy or intolerance to beef or to any ingredient in the product.
Subject has active drug or alcohol abuse that in the opinion of the investigator may interfere with the subject's ability to comply with this protocol.
History of uncontrolled psychiatric disorders (includes significant depression or suicidal ideation), that in the opinion of the investigator may interfere with the subject's ability to comply with this protocol.
In the opinion of the investigator, progression to death is imminent and highly likely within the next 24 hours.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roberto Güerri Fernández, MD, PhD
Organizational Affiliation
Hospital del Mar (Barcelona, Spain)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Netanya S. Utay, MD
Organizational Affiliation
University of Texas Health Science Center at Houston (Houston, TX, USA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Evaluating the Impact of EnteraGam In People With COVID-19
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