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Covid19PICNICNCT04682041

Evaluating the Impact of EnteraGam In People With COVID-19

A study testing Bovine Plasma-Derived Immunoglobulin Concentrate in people with Covid19, run by Entera Health, Inc at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19
What is being tested?
Bovine Plasma-Derived Immunoglobulin Concentrate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
1 siteSpain
Study dates
22 Dec 2020to 21 Feb 2022
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

  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

Spain1 site
  • Hospital del Mar

    Barcelona, 08003

Other trials in Spain

About this study

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

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.

Read more

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.

Read the 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).

Conditions
Covid19
Being tested
Bovine Plasma-Derived Immunoglobulin Concentrate, Standard of care
Keywords
SARS-CoV-2, Coronavirus, Bovine Plasma-Derived Immunoglobulin
Medical subject headings
COVID-19, Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bovine Plasma-Derived Immunoglobulin ConcentrateDietary supplement

    Also called EnteraGam®

    EnteraGam® 10.0 g, containing 5.0 g of serum-derived bovine immunoglobulin/protein isolate (SBI) BID (every 12 hours) for 2 weeks.

  • Standard of careOther

    Standard of care PSMAR protocol for COVID-19 patients.

Study groups in NCT04682041
Study groupRoleWhat they receive
EnteraGam + standard of careExperimentalSubjects 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.
Receives: Dietary Supplement: Bovine Plasma-Derived Immunoglobulin Concentrate; Other: Standard of care
Control (standard of care)OtherSubjects will receive standard of care for COVID-19 alone for 2 weeks. Total study duration (including the screening phase) will be approximately 4 weeks.
Receives: Other: Standard of care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in plasma IL-6 levels

    Variation of IL-6 levels measured in plasma

    Measured: From baseline to Week 2

  2. COVID-19 disease progression by Week 2

    Percentage of patients with COVID-19 who have disease progression by Week 2, defined as:

    1. 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.
    2. For inpatients, worsening of ≥1 level on the WHO 9-point ordinal scale.

    Measured: From baseline to Week 2

Secondary outcomes (13)
  1. Change in dyspnea

    Variation of dyspnea presentation at Week 2 compared to baseline, assessed by daily symptoms questionnaire

    Measured: At Week 2

  2. Change in diarrhea

    Variation of diarrhea presentation at Week 2 compared to baseline, assessed by daily symptoms questionnaire

    Measured: At Week 2

  3. Change in fever

    Variation of fever presentation at Week 2 compared to baseline

    Measured: At Week 2

  4. Change in neutrophil count

    Variation of neutrophil count at Week 2 compared to baseline

    Measured: At Week 2

  5. Change in lymphocyte count

    Variation of lymphocyte count at Week 2 compared to baseline

    Measured: At Week 2

  6. Change in neutrophil/lymphocyte ratio

    Variation of neutrophil/lymphocyte ratio at Week 2 compared to baseline

    Measured: At Week 2

  7. Change in platelet count

    Variation of platelet count at Week 2 compared to baseline

    Measured: At Week 2

  8. Change in C-reactive protein

    Variation of C-reactive protein levels at Week 2 compared to baseline

    Measured: At Week 2

  9. Change in ferritin

    Variation of ferritin levels at Week 2 compared to baseline

    Measured: At Week 2

  10. Change in D-dimer

    Variation of D-dimer levels at Week 2 compared to baseline

    Measured: At Week 2

  11. Change in AST

    Variation of Aspartate Transaminase (AST/GOT) levels at Week 2 compared to baseline

    Measured: At Week 2

  12. Change in ALT

    Variation of Alanine Transaminase (ALT/GPT) levels at Week 2 compared to baseline

    Measured: At Week 2

  13. Time to worsening clinical status

    Time elapsed between baseline and disease progression, defined as:

    1. For outpatients, return to emergency department for COVID-19 related manifestations or worsening of ≥1 level on the WHO 9-point ordinal scale.
    2. For inpatients, worsening of ≥1 level on the WHO 9-point ordinal scale.

    Measured: From baseline to Week 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2020
  2. Study start22 Dec 2020
  3. Primary completion20 Dec 2021
  4. Study completion21 Feb 2022

Resources

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
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)
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04682041
Sponsor's protocol ID
PICNIC Study
Acronym
PICNIC
Status last verified
Apr 2023
First submitted
18 Dec 2020
Last updated
20 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Bovine Plasma-Derived Immunoglobulin Concentrate in people with Covid19, run by Entera Health, Inc at 1 site in Spain.

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 8 inclusion and 10 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 20 Apr 2023. 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 Spain. 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?

Change in plasma IL-6 levels (time frame: From baseline to Week 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 20 Apr 2023.

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