Inhaled Aviptadil for the Treatment of COVID-19 in Patients at High Risk for ARDS

January 16, 2024 updated by: Prof. Dr. Jörg Leuppi

Inhaled Aviptadil for the Treatment of COVID-19 in Patients at High Risk for ARDS: A Randomized, Placebo Controlled, Multicenter Trial

The world is currently experiencing a coronavirus (CoV-2) pandemic. A new (SARS)-CoV infection epidemic began in Wuhan, Hubei, China, in late 2019; originally called 2019- nCoV the virus is now known as SARSCoV- 2 and the disease it causes COVID-19. Previous CoV epidemics included severe acute respiratory syndrome (SARS)-CoV, which started in China in 2003 and Middle East respiratory syndrome (MERS)-CoV in the Middle East, which started in 2012. The mortality rates were >10% for SARS and >35% for MERS. The direct cause of death is generally due to ensuing severe atypical pneumonia and ensuing acute respiratory distress syndrome (ARDS). Pneumonia also is generally the cause of death for people who develop influenza, although the mortality rate is lower (1%-3% for the influenza A H5N1 pandemic of 1918-1919 in the United States). Risk factors for a poor outcome of SARS-CoV-2 infection have so far been found to include older age and co-morbidities including chronic cardiovascular and respiratory conditions and current smoking status. In May 2020, the FDA authorized the emergency use of remdesivir for treatment of COVID-19 disease based on topline date of two clinical trials, even though an underpowered clinical trial did not find significant improvement in COVID- 19 patients treated with remdesivir. Nevertheless, remdesivir is the first and so far, only approved treatment for COVID-19. Additionally further trials and clinical observations have not found a significant benefit of other antiviral drugs. Although the results of several studies are still pending, there is still a desperate need for an effective, safe treatment for COVID-19. Aviptadil, which is a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP), might be beneficial in patients at risk of developing ARDS. Nonclinical studies demonstrate that VIP is highly concentrated in the lung, where it reduces inflammation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

About 20% of individuals with Corona Virus disease (COVID-19) experience more severe disease characterized by significant respiratory symptoms including acute respiratory distress syndrome (ARDS). ARDS is a known lethal complication due to its low blood oxygenation levels and may result in organ failure. Until now, there are no specific vaccines or therapeutic drugs targeting SARS-CoV-2, alternative therapeutic interventions are needed to prevent and ameliorate respiratory conditions associated with COVID-19 to effectively reduce mortality and prevent ICU admissions. Aviptadil, which is a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP), might be beneficial in patients at risk of developing ARDS. Nonclinical studies demonstrate that VIP is highly concentrated in the lung, where it prevents N-methyl-D-aspartate (NMDA)-induced caspase-3 activation, inhibits IL-6 and TNFa production and protects against HCl-induced pulmonary edema. Further, in animal model systems of lung injury in mice, rats, guinea pigs, sheep, swine and dogs, Aviptadil was shown to restore barrier function at the endothelial/alveolar interface and to protect the lung and other organs from failure. In Europe, Aviptadil is approved for human use and has been shown to be safe in phase II trials for sarcoidosis, pulmonary fibrosis, bronchospasm, erectile dysfunction as well as in a phase I trial in ARDS in the past two decades. In the US, VIP has been given FDA Orphan Drug Designation for the treatment of ARDS and was admitted to the FDA Corona Virus Technology Accelerator Program. In a phase I trial of Aviptadil performed by Sami Said in the early 2000s, eight patients with severe ARDS on mechanical ventilation were treated with ascending doses of intravenous VIP. Seven patients (88%) were successfully extubated and were alive at the five day time point. Six (75%) left the hospital and one (13%) died of an unrelated cardiac event. A phase II clinical trial using intravenous Aviptadil in patients with COVID-19 infection and ARDS has begun. Further, a phase II/III clinical trial will study the effect of inhaled Aviptadil for the treatment of non-acute lung injury in COVID- 19 and begins in June 2020. In Europe, two phase II trials of Aviptadil have been conducted. Further, studies with healthy volunteers have shown that inhaled Aviptadil is well tolerated with few adverse effects.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
83

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • St.Gallen, Switzerland, 9007
        • Cantonal Hospital St.Gallen
    • BL
      • Liestal, BL, Switzerland, 4410
        • Cantonal Hospital Baselland Liestal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • COVID-19 infection diagnosed
  • Risk factors for the development of an ARDS according to an adapted EALI (early acute lung injury score) ≥ 2 Points (with at least one point from the EALI score)

EALI Score:

  • 2-6l O2 supplementation to achieve a SaO2>90%: 1 point
  • >6l O2 supplementation to achieve a SaO2>90%: 2 points
  • Respiratory rate ≥ 30/min: 1 point
  • Immunosuppression: 1 Point

Modification (for adapting for risk factors for ARDS in SARS-CoV-2 affected patients

  • Arterial hypertension: 1 point
  • Diabetes: 1 point

  • Fever > 39°C: 1 point

    • Age > 18 years
    • Ability to adequate compliance with the inhalation manoeuvre
    • Ability to sign the informed consent

Exclusion Criteria:

  • Known or highly suspected bacterial infection (antibiotic treatment to avoid bacterial superinfection may be allowed)
  • PCT ≥ 1μg/l
  • Mechanical ventilation
  • Inability to conduct inhalation therapy
  • Hemodynamic instability with requirement of vasopressor therapy
  • Severe comorbidities interfering with the safe participation at the trial according to the treating physician
  • Pregnancy
  • Systemic immunosuppression

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Aviptadil Treatment
Participants will receive standard care plus a dose of 67μg nebulized Aviptadil three times a day for ten days.
Drug: Aviptadil 67μg
Participants will receive standard care plus a dose of 67μg nebulized Aviptadil three times a day for ten days.
Placebo Comparator: Placebo Treatment
Participants in the control group will receive an Inhalation of 0.9% NaCl solution three times a day for 10 days
Drug: Placebo 0.9% NaCl solution
Patiens will receive Standard care plus 0.9% NaCl solution three times a day for ten days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to clinical improvement
Time Frame: Randomization until discharge from hospital but up to maximum 28 days

Time to clinical improvement of a decrease of at least two points on a seven-point ordinal scale of clinical status or discharged alive from hospital. The seven-point scale consists of the following categories:

  1. not hospitalized;
  2. hospitalized, not requiring supplemental oxygen;
  3. hospitalized, requiring supplemental oxygen;
  4. hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both;
  5. hospitalized, intubation and mechanical ventilation;
  6. ventilation and additional organ support - pressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO);
  7. death
Randomization until discharge from hospital but up to maximum 28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Frequency of mechanical ventilation
Time Frame: Randomization until discharge from hospital up to maximum 28 days
Frequency of Patient who need mechanical ventilation during hospital stay
Randomization until discharge from hospital up to maximum 28 days
Oxygen supplementation
Time Frame: Randomization until discharge from hospital up to maximum 28 days
Time requiring oxygen supplementation
Randomization until discharge from hospital up to maximum 28 days
SaO2
Time Frame: Randomization until discharge from hospital up to maximum 28 days
Slope in SaO2
Randomization until discharge from hospital up to maximum 28 days
FiO2
Time Frame: Randomization until discharge from hospital but up to maximum 28 days
Slope in FiO2
Randomization until discharge from hospital but up to maximum 28 days
C-reactive Protein
Time Frame: measured at baseline, at least every 7 days and at discharge up to maximum 28 days
Slope in C-reactive Protein
measured at baseline, at least every 7 days and at discharge up to maximum 28 days
Neutrophile
Time Frame: measured at baseline, at least every 7 days and at discharge up to maximum 28 days
Neutrophile ratio
measured at baseline, at least every 7 days and at discharge up to maximum 28 days
lymphocyte
Time Frame: measured at baseline, at least every 7 days and at discharge up to maximum 28 days
lymphocyte ratio
measured at baseline, at least every 7 days and at discharge up to maximum 28 days
Interleukine 6
Time Frame: measured at baseline, at least every 7 days and at discharge up to maximum 28 days
Interleukine 6 level
measured at baseline, at least every 7 days and at discharge up to maximum 28 days
Procalcitonin
Time Frame: measured at baseline, at least every 7 days and at discharge up to maximum 28 days
Procalcitonin level
measured at baseline, at least every 7 days and at discharge up to maximum 28 days
Frequency of Multi organ dysfunction Syndrome (MODS)
Time Frame: Randomization until discharge from hospital up to maximum 28 days
Frequency of Patient who showed a multi organ dysfunction Syndrome during Hospital stay
Randomization until discharge from hospital up to maximum 28 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospitalization
Time Frame: randomization till discharge of hospital up to 28 days
duration of hospitalization in survivors
randomization till discharge of hospital up to 28 days
treatment initiation to death
Time Frame: Treatment initiation to death up to maximum 28 days
Time from treatment initiation to death
Treatment initiation to death up to maximum 28 days
Blood pressure
Time Frame: Daily until discharge up to maximum 28 days
Blood pressure will be assessed daily in mmHg
Daily until discharge up to maximum 28 days
Heart rate
Time Frame: Daily until discharge up to maximum 28 days
Heart rate will be assessed daily in bpm
Daily until discharge up to maximum 28 days
Respiratory rate
Time Frame: Daily until discharge up to maximum 28 days
Respiratory rate will be assessed daily in Counts per minute
Daily until discharge up to maximum 28 days
Body temperature (auricular) in °C
Time Frame: Daily until discharge up to maximum 28 days
Body temperature (auricular) will be assessed daily in °C
Daily until discharge up to maximum 28 days
Pulse oximetry
Time Frame: Daily until discharge up to maximum 28 days
Pulse oximetry will be assessed daily in %
Daily until discharge up to maximum 28 days
Glasgow Coma Scale
Time Frame: Daily until discharge up to maximum 28 days
Glasgow Coma Scale will be assessed daily The lowes possible score is 3 = deep coma or death The highest possible score is 15 = Fully awake
Daily until discharge up to maximum 28 days
Dispnea and caugh
Time Frame: Randomization until discharge from hospital up to maximum 28 days
Visual analogue scale for dyspnea and cough as patient-related outcome parameter
Randomization until discharge from hospital up to maximum 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Prof. Dr. Jörg Leuppi

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jörg D Leuppi, Professor, Cantonal Hosptal, Baselland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 18, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 14, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 14, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 21, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 2, 2020

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 18, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020-01902

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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