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Trial record 6 of 7 for:    Aviptadil

ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 (TESICO)

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ClinicalTrials.gov Identifier: NCT04843761
Recruitment Status : Recruiting
First Posted : April 14, 2021
Last Update Posted : October 26, 2021
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
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
Covid19 Biological: Remdesivir Drug: Remdesivir Placebo Biological: Aviptadil Drug: Aviptadil Placebo Drug: Corticosteroid Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 640 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : April 20, 2021
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : April 2023


Arm Intervention/treatment
Experimental: Aviptadil + Remdesivir + 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 + 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: Aviptadil Placebo + 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: 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: Aviptadil Placebo + Remdesivir Placebo + SOC Drug: Remdesivir Placebo
Commercially available 0.9% sodium chloride solution. Administered by IV infusion daily for 10 days.

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.




Primary Outcome Measures :
  1. Recovery, assessed at 90 days [ Time Frame: Thru Day 90 ]
    Recovery categorized as 1 (Best): At home and not receiving new supplemental oxygen for ≥ 77 consecutive days; 2: At home and not receiving new supplemental oxygen for 49-76 consecutive days; 3: At home and not receiving new supplemental oxygen for 1-48 consecutive days; 4: Discharged from hospital but either not yet home or home but receiving new supplemental oxygen; 5: Still hospitalized or receiving hospice care; 6 (Worst): Dead.


Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: Thru Day 90 ]
  2. Time to death [ Time Frame: Thru Day 90 ]
  3. Composite of time to recovery, days at home off new supplemental oxygen and time to death [ Time Frame: Thru Day 90 ]
    Measured in number of days

  4. Composite of alive, at home and off new supplemental oxygen [ Time Frame: Thru Day 90 ]
  5. Composite of recovered, alive and not recovered, and dead [ Time Frame: Thru Day 90 ]
    Recovery defined as alive, at home and off new supplemental oxygen

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

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

  8. Incidence of clinical organ failure or serious infections [ Time Frame: Thru Day 28 ]
    Defined as any one or more of: Worsening respiratory dysfunction; cardiac and vascular dysfunction; renal dysfunction; hepatic dysfunction; neurological dysfunction, haematological dysfunction; serious infection

  9. Composite of death, clinical organ failure or serious infections [ Time Frame: Thru Day 90 ]
  10. Composite of cardiovascular events and thromboembolic events [ Time Frame: Thru Day 28 ]
  11. Composite of cardiovascular events and thromboembolic events [ Time Frame: Thru Day 90 ]
  12. Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death [ Time Frame: Thru Days 5 and 28 ]
  13. Incidence of infusion reactions [ Time Frame: Thru Day 180 ]
  14. Percentage of participants for whom infusion was interrupted or stopped prior to completion for any reason [ Time Frame: Thru Day 90 ]
  15. Percentage of participants for whom infusion was interrupted or stopped prior to completion due to adverse event [ Time Frame: Thru Day 90 ]
  16. Composite of hospital readmissions or death [ Time Frame: Thru Day 180 ]
  17. Incidence of no home use of supplemental oxygen above pre-morbid oxygen use [ Time Frame: 14 days ]
    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.

  18. Time to hospital discharge from initial hospitalization [ Time Frame: Thru Day 180 ]
  19. Composite of death or serious clinical COVID-19 related events [ Time Frame: Thru Day 90 ]
  20. Pulmonary ordinal outcome [ Time Frame: Days 1-7, 14 and 28 ]
    Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

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

  23. In category 4, 5 or 6 at Day 90 vs. in categories 1-3 at Day 90 [ Time Frame: 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.

  24. In category 5 or 6 at Day 90 vs. in categories 1-4 at Day 90 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04843761


Contacts
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Contact: If interested in participating in this study, please contact the appropriate site or send email to tesico@insight-trials.org
Contact: Do not include personal information in email. Type ACTIV-3b in subject line.

Locations
Show Show 39 study locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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
Investigators
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Principal Investigator: Samuel Brown, MD Intermountain Medical Center/University of Utah
Study Chair: Prof. James Neaton INSIGHT Statistical and Coordinating Centre, University of Minnesota
Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04843761    
Other Study ID Numbers: 015 / ACTIV-3b
First Posted: April 14, 2021    Key Record Dates
Last Update Posted: October 26, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
COVID-19
COVID 19
Coronaviridae Infections
Coronavirus Infections
RNA Virus Infections
Virus Diseases
Nidovirales Infections
SARS-CoV-2
SARS Coronavirus
ACTIV-3
ACTIV3
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Remdesivir
Phentolamine
Vasoactive Intestinal Peptide
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antihypertensive Agents
Gastrointestinal Agents
Vasodilator Agents
Neuroprotective Agents
Protective Agents