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History of Changes for Study: NCT04843761
ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 (TESICO)
Latest version (submitted June 11, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 9, 2021 None (earliest Version on record)
2 April 16, 2021 Recruitment Status, Arms and Interventions, Outcome Measures, Contacts/Locations, Study Status and Sponsor/Collaborators
3 April 21, 2021 Study Status and Contacts/Locations
4 April 23, 2021 Contacts/Locations and Study Status
5 April 27, 2021 Contacts/Locations and Study Status
6 April 30, 2021 Contacts/Locations and Study Status
7 May 7, 2021 Contacts/Locations and Study Status
8 May 14, 2021 Contacts/Locations and Study Status
9 May 21, 2021 Contacts/Locations and Study Status
10 May 27, 2021 Contacts/Locations and Study Status
11 June 4, 2021 Study Status and Contacts/Locations
12 June 11, 2021 Contacts/Locations and Study Status
Comparison Format:

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Changes (Merged) for Study: NCT04843761
April 9, 2021 (v1) -- April 16, 2021 (v2)

Changes in: Study Status, Sponsor/Collaborators, Arms and Interventions, Outcome Measures and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: 015 / ACTIV-3b
Brief Title: ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 (TESICO)
Official Title: A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With Acute Respiratory Distress Syndrome Associated With COVID-19
Secondary IDs:
Open or close this module Study Status
Record Verification: April 2021
Overall Status: Not yet Recruiting
Study Start: April 2021
Primary Completion: October 2022 [Anticipated]
Study Completion: April 2023 [Anticipated]
First Submitted: April 9, 2021
First Submitted that
Met QC Criteria:
April 9, 2021
First Posted: April 14, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
April 9 16, 2021
Last Update Posted: April 14 19, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Responsible Party: Sponsor
Collaborators: International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
University of Copenhagen
Medical Research Council
Kirby Institute
Washington D.C. Veterans Affairs Medical Center
AIDS Clinical Trials Group
National Heart, Lung, and Blood Institute (NHLBI)
US Department of Veterans Affairs
Prevention and Early Treatment of Acute Lung Injury (PETAL)
Cardiothoracic Surgical Trials Network (CTSN)
NeuroRx, Inc.
Gilead Sciences
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection and who have acute respiratory failure. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.
Detailed Description:

This is a master protocol to evaluate the safety and efficacy of investigational agents aimed at improving outcomes for patients with acute respiratory failure related to COVID-19.

Trials within this protocol will be adaptive, randomized, blinded and initially placebo-controlled. Participants will receive standard of care (SOC) treatment as part of the protocol. If an investigational agent shows superiority over placebo, SOC for the study of future investigational agents may be modified accordingly.

The international trials within this protocol will be conducted in up to several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.

The protocol is for a phase III platform study that allows investigational drugs to be added and dropped during the course of the study. This allows for efficient testing of new drugs against control within the same trial infrastructure. When more than one agent is being tested concurrently, participants may be randomly allocated across agents (as well as between the agent and its placebo) so the same control group can be shared, when feasible. In some situations, a factorial design may be used to study multiple agents.

Participants will be followed for 90 days following randomization for the primary endpoint and most secondary endpoints. Selected secondary endpoints will be measured at 180 days.

This study is planned to provide 80% power to detect an odds ratio of 1.5 for improvement in recovery status at Day 90 for an investigational agent versus placebo with use of the ordinal outcome. The planned sample size is 640 participants (320 per group) for each investigational agent/placebo. Sample size may be re-estimated before enrollment is complete based on an assessment of whether the pooled proportions of the outcome are still consistent with adequate power for the hypothesized difference measured by the odds ratio.

Randomization will be stratified by study site pharmacy and by receipt of invasive mechanical ventilation, or ECMO at enrollment. Other agent-specific stratification factors may be considered.

Investigational agents suitable for testing in the inpatient setting will be prioritized based on in vitro data, preclinical data, phase I pharmacokinetic and safety data, and clinical data from completed and ongoing trials. In some cases, a vanguard cohort/initial pilot phase may be incorporated into the trial.

An independent Data and Safety Monitoring Board (DSMB) will review interim safety and efficacy data at least monthly. Pre-specified guidelines will be established to recommend early stopping of the trial for evidence of harm or substantial efficacy. The DSMB may recommend discontinuation of an investigational agent if the risks are judged to outweigh the benefits.

Open or close this module Conditions
Conditions: Covid19
Keywords: COVID-19
COVID 19
Coronaviridae Infections
Coronavirus Infections
RNA Virus Infections
Virus Diseases
Nidovirales Infections
SARS-CoV-2
SARS Coronavirus
ACTIV-3
ACTIV3
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 4
Masking: Triple (Participant, Care Provider, Investigator)
Allocation: Randomized
Enrollment: 640 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Aviptadil + Remdesivir plus + SOC Biological: Remdesivir
Administered by IV infusion, daily for 10 days. Initial loading dose is 200 mg with all subsequent doses 100 mg.
Biological: Aviptadil
Administered by IV infusion over 12 hours per day for 3 days.
Other Names:
  • Vasoactive Intestinal Peptide
  • VIP
Drug: Corticosteroid
In line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone, methylprednisolone or hydrocortisone may be administered as SOC.
Placebo Comparator: Aviptadil + Remdesivir Placebo plus + SOC Drug: Remdesivir Placebo
Commercially available 0.9% sodium chloride solution. Administered by IV infusion daily for 10 days.
Biological: Aviptadil
Administered by IV infusion over 12 hours per day for 3 days.
Other Names:
  • Vasoactive Intestinal Peptide
  • VIP
Drug: Corticosteroid
In line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone, methylprednisolone or hydrocortisone may be administered as SOC.
Experimental: VIP Aviptadil Placebo plus + Remdesivir + SOC Biological: Remdesivir
Administered by IV infusion, daily for 10 days. Initial loading dose is 200 mg with all subsequent doses 100 mg.
Drug: VIP Aviptadil Placebo
Commercially available 0.9% sodium chloride solution. Administered by IV infusion over 12 hours per day for 3 days.
Drug: Corticosteroid
In line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone, methylprednisolone or hydrocortisone may be administered as SOC.
Experimental: VIP plus SOC Experimental: Aviptadil Placebo + Remdesivir Placebo + SOC Drug: Remdesivir Placebo
Commercially available 0.9% sodium chloride solution. Administered by IV infusion daily for 10 days.
Biological: VIP
Administered by IV infusion over 12 hours per day for 3 days.
Other Names:
  • Vasoactive Intestinal Peptide
  • aviptadil
Drug: Aviptadil Placebo
Commercially available 0.9% sodium chloride solution. Administered by IV infusion over 12 hours per day for 3 days.
Drug: Corticosteroid
In line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone, methylprednisolone or hydrocortisone may be administered as SOC.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Time to recovery Recovery, assessed at 90 days
Recovery categorized as 1 (Best): At home an off oxygen for ≥ 77 consecutive days; 2: At home and off oxygen for 49-76 consecutive days; 3: At home and off oxygen for 1-48 consecutive days; 4: Not hospitalized and either at home on oxygen or not at home; 5: Hospitalized for medical care or in hospice care; 6 (Worst): Dead.

[Time Frame: Thru Day 90]
Secondary Outcome Measures:
2. All-cause mortality

[Time Frame: Thru Day 90]
3. Composite of time to recovery, free/not free of respiratory support and mortality

[Time Frame: Thru Day 90]
4. Time from randomization to recovery
Recovery defined as alive, at home and off oxygen (treating death as competing risk)

[Time Frame: Thru Day 90]
5. Days alive outside short-term acute care hospital
Using "last off" method.

[Time Frame: Up to Day 90]
6. Incidence of clinical organ failure

[Time Frame: Thru Day 28]
7. Composite of death, clinical organ failure or serious infections

[Time Frame: Thru Day 90]
8. Composite of cardiovascular events and thromboembolic events

[Time Frame: Thru Day 90]
9. Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death

[Time Frame: Thru Days 5 and 28]
10. Incidence of infusion reactions

[Time Frame: Thru Day 180]
11. Percentage of participants for whom infusion was interrupted or stopped prior to completion for any reason

[Time Frame: Thru Day 90]
12. Percentage of participants for whom infusion was interrupted or stopped prior to completion due to adverse event

[Time Frame: Thru Day 90]
13. Composite of hospital readmissions or death

[Time Frame: Thru Day 180]
14. Incidence of no home use of supplemental oxygen above pre-morbid oxygen use
Measured as: Alive at home for an uninterrupted 14 day period and no use of continuous supplemental oxygen at end of 14 day time period.

[Time Frame: 14 days]
15. Time to hospital discharge from initial hospitalization

[Time Frame: Thru Day 180]
16. Composite of death or serious clinical COVID-19 related events

[Time Frame: Thru Day 90]
17. Pulmonary ordinal outcome
Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

[Time Frame: Days 1-7, 14 and 28]
18. Pulmonary+ ordinal outcome
Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

[Time Frame: Days 1-7 ]
19. Composite of SAEs or death

[Time Frame: Thru Day 180]
20. Change in SARS-CoV-2 neutralizing antibody levels

[Time Frame: Baseline to Days 1, 3, 5, 28 and 90 ]
21. Incidence of home use of supplemental oxygen above pre-morbid oxygen use
Measured as: Alive at home and no use of continuous supplemental oxygen for an uninterrupted 14 day period

[Time Frame: Thru Day 180]
22. Change in neutralizing antibody levels In category 4, 5 or 6 at Day 90 vs. in categories 1-3 at Day 90
Categories are 1 (Best): At home an off oxygen for ≥ 77 consecutive days; 2: At home and off oxygen for 49-76 consecutive days; 3: At home and off oxygen for 1-48 consecutive days; 4: Not hospitalized and either at home on oxygen or not at home; 5: Hospitalized for medical care or in hospice care; 6 (Worst): Dead.

[Time Frame: Baseline to Days 1, 3, 5, 28 and 90 Day 90]
23. Change in overall titers of antibodies In category 5 or 6 at Day 90 vs. in categories 1-4 at Day 90
Categories are 1 (Best): At home an off oxygen for ≥ 77 consecutive days; 2: At home and off oxygen for 49-76 consecutive days; 3: At home and off oxygen for 1-48 consecutive days; 4: Not hospitalized and either at home on oxygen or not at home; 5: Hospitalized for medical care or in hospice care; 6 (Worst): Dead.

[Time Frame: Baseline to Days 1, 3, 5, 28 and 90 Day 90]
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Signed informed consent.
  • Requiring admission to hospital for acute medical care (not for purely public health or quarantine purposes).
  • Current respiratory failure (i.e. receipt of high-flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation, or ECMO (extracorporeal membrane oxygenation) used to treat acute hypoxemic respiratory failure).
  • SARS-CoV-2 (COVID-19) infection, documented by a nucleic acid test (NAT) or equivalent testing with most recent rest within 14 days prior to randomization.
  • Respiratory failure is believed to be due to SARS-CoV-2 pneumonia.

Exclusion Criteria:

  • Known allergy to investigational agent or vehicle.
  • More than 4 days since initiation of support for respiratory failure.
  • Chronic/home mechanical ventilation (invasive or non-invasive) for chronic lung or neuromuscular disease (non-invasive ventilation used solely for sleep-disordered breathing is not an exclusion).
  • Moribund patient (i.e. not expected to survive 24 hours).
  • Active use of "comfort care" or other hospice-equivalent standard of care.
  • Expected inability to participate in study procedures.
  • In the opinion of the investigator, any condition for which, participation would not be in the best interest of the participant or that could limit protocol-specified assessments.
  • Previous enrollment in TESICO

Agent-specific exclusion criteria

  • Prior receipt of any dose of remdesivir during present illness (remdesivir agent).
  • GFR (glomerular filtration rate) < 30 ml/min and not receiving dialysis (remdesivir agent).
  • ALT (alanine aminotransferase) or AST (aspartate aminotransferase) > 10 times upper limit of normal (remdesivir agent).
  • Unwillingness to commit to avoid sex that may result in pregnancy for at least 7 days after completion of remdesivir vs. placebo (remdesivir agent).
  • Refractory hypotension (aviptadil agent).
  • Severe diarrhea (Aviptadil agent).
  • Current C. difficile infection (aviptadil agent).
  • Pregnancy or current breast-feeding (aviptadil agent).
  • End-stage liver disease (aviptadil agent).
Open or close this module Contacts/Locations
Central Contact Person: If interested in participating in this study, please contact the appropriate site or
Telephone: send email to
Email: tico tesico@insight-trials.org
Central Contact Backup: Do not include personal information in email. Type ACTIV-3b in subject line.
Study Officials: Samuel Brown, MD
Principal Investigator
Intermountain Medical Center/University of Utah
Prof. James Neaton
Study Chair
INSIGHT Statistical and Coordinating Centre, University of Minnesota
Locations: United States, North Carolina
Duke University Hospital (Site 301-006), 2301 Erwin Road
[Recruiting]
Durham, North Carolina, United States, 27710
Contact:Contact: If interested in participating at this site, enter site name and ACTIV-3b in subject line of email and send to ticoctsn@insight-trials.org
Contact:Contact: Do not include personal information in email
United States, Utah
University of Utah Health (Site 211-002), 419 Wakara Way, Ste. 207
[Not yet recruiting]
Salt Lake City, Utah, United States, 84108
Contact:Contact: If interested in participating at this site, enter site name and ACTIV-3b in subject line of email and send to ticopetal@insight-trials.org
Contact:Contact: Do not include personal information in email
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Open or close this module References
Citations:
Links: Description: FDA Safety Alerts and Recalls
Description: CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website
Description: A Participant's Guide to Clinical Trials (NIAID)
Description: Find a Clinical Trial (NIAID)
Description: Clinical Trials at NIAID
Description: National Institute for Allergy and Infectious Diseases (NIAID)
Description: NIH COVID-19 treatment guidelines
Description: WHO COVID-19 treatment guidelines
Available IPD/Information:

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