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

NCT04536350 | Terminated Phase 2

• 1 other identifier: 2020-01902
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Covid19; Corona Virus Infection; ARDS; Aviptadil

Keywords

Covid 19; Corona Virus Infection; acute respiratory distress syndrome (ARDS); Aviptadil; Faster recovery

Outcome Measures

Primary Outcomes (1)

• Time to clinical improvement

  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 Outcomes (10)

• Frequency of mechanical ventilation

  Randomization until discharge from hospital up to maximum 28 days

• Oxygen supplementation

  Randomization until discharge from hospital up to maximum 28 days

• SaO2

  Randomization until discharge from hospital up to maximum 28 days

• FiO2

  Randomization until discharge from hospital but up to maximum 28 days

• C-reactive Protein

  measured at baseline, at least every 7 days and at discharge up to maximum 28 days

Other Outcomes (9)

• Hospitalization

  randomization till discharge of hospital up to 28 days

• treatment initiation to death

  Treatment initiation to death up to maximum 28 days

• Blood pressure

  Daily until discharge up to maximum 28 days

Study Arms (2)

Aviptadil Treatment

EXPERIMENTAL

Participants will receive standard care plus a dose of 67μg nebulized Aviptadil three times a day for ten days.

Drug: Aviptadil 67μg

Placebo Treatment

PLACEBO COMPARATOR

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

Interventions

Aviptadil 67μg DRUG

Participants will receive standard care plus a dose of 67μg nebulized Aviptadil three times a day for ten days.

Aviptadil Treatment

Placebo 0.9% NaCl solution DRUG

Patiens will receive Standard care plus 0.9% NaCl solution three times a day for ten days

Placebo Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• l 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prof. Dr. Jörg Leuppi: lead

Study Sites (2)

Cantonal Hospital Baselland Liestal

Liestal, Basel-Landschaft, 4410, Switzerland

Location

Cantonal Hospital St.Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (1)

• Boesing M, Abig K, Brandle M, Brutsche M, Burri E, Frye BC, Giezendanner S, Grutters JC, Haas P, Heisler J, Jaun F, Leuppi-Taegtmeyer AB, Luthi-Corridori G, Muller-Quernheim J, Nuesch R, Pohl W, Rassouli F, Leuppi JD. Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial. Trials. 2022 Sep 20;23(1):790. doi: 10.1186/s13063-022-06723-w.

  PMID: 36127739 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Respiratory Distress Syndrome

Interventions

aviptadil

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Jörg D Leuppi, Professor

  Cantonal Hosptal, Baselland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Patients and the investigator administering inhalation devices of drug or placebo are not aware of which group they have been randomized to (double-blinded). Someone not involved in the study (e.g. the hospital pharmacist or a nurse not involved in study) prepares the inhalation devices with either drug or placebo according to the randomization plan received by the CTU
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Internal Medicine

Model Details: Patients will be randomly allocated to receive either Aviptadil together with standard care or the placebo (NaCl 0.9%) together with standard care,

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: September 2, 2020
• Study Start: May 18, 2021
• Primary Completion: June 14, 2023
• Study Completion: June 14, 2023
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)