Bevacizumab for Acute Respiratory Distress Syndrome

Recruiting at 27 trial locations

Overseen By Just Breathe Trial Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: PPD DEVELOPMENT, LP

Must not be taking: Aspirin, Clopidogrel, DOACs

Disqualifiers: Cirrhosis, Dialysis, Hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: In-hospital stay

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called bevacizumab, a monoclonal antibody, to determine its effectiveness for hospitalized patients with Acute Respiratory Distress Syndrome (ARDS), which impairs breathing. Researchers aim to assess the safety and efficacy of this treatment compared to a placebo, which contains no active medicine. Participants will receive either bevacizumab or a placebo. The trial seeks participants with ARDS who are hospitalized but excludes those with conditions like uncontrolled high blood pressure or recent serious bleeding. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but it does mention that participants on anticoagulants must have stable doses for at least 2 weeks before starting the study. Also, certain medications like high-dose aspirin or specific anticoagulants without reversal agents may need to be stopped.

Is there any evidence suggesting that bevacizumab is likely to be safe for humans?

Research has shown that bevacizumab, a treatment under study for Acute Respiratory Distress Syndrome (ARDS), demonstrated promise in earlier studies. In animal studies, bevacizumab reduced fluid buildup in the lungs, a major issue in ARDS, suggesting the drug might improve lung function.

Regarding safety, previous studies of bevacizumab for other conditions provide some insights. The FDA has already approved bevacizumab for treating certain cancers, indicating a known safety profile. However, side effects can occur, with common ones in other uses including high blood pressure and bleeding.

The current study is in Phase 2, focusing on both safety and effectiveness. This phase usually involves more participants than earlier studies, offering researchers a clearer picture of potential side effects in a larger group. While bevacizumab has been used safely for other conditions, monitoring its effects specifically in ARDS patients remains important. This trial aims to gather data on that. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ARDS?

Bevacizumab is unique because it targets vascular endothelial growth factor (VEGF), a protein that plays a key role in blood vessel formation and inflammation, which are critical factors in acute respiratory distress syndrome (ARDS). Unlike the standard of care treatments for ARDS, which mainly focus on supportive care like mechanical ventilation and corticosteroids to reduce inflammation, bevacizumab offers a targeted approach by inhibiting VEGF. Researchers are excited about this treatment because it has the potential to directly address the underlying processes driving ARDS, possibly leading to improved outcomes and faster recovery compared to existing therapies.

What evidence suggests that bevacizumab might be an effective treatment for ARDS?

Research has shown that bevacizumab, initially used for certain cancers, might help people with Acute Respiratory Distress Syndrome (ARDS) breathe more easily. Studies have found that bevacizumab can improve oxygen levels and shorten the duration of oxygen support. Specifically, some research suggests it could reduce the death rate in ARDS caused by COVID-19. By blocking a protein that promotes blood vessel growth, bevacizumab helps reduce lung fluid, easing breathing. This trial will compare bevacizumab with a placebo to evaluate its effectiveness in treating ARDS. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for hospitalized adults with Acute Respiratory Distress Syndrome (ARDS). Participants must meet additional criteria not specified here to join. People who don't fit the inclusion criteria or meet any exclusion factors can't participate.

Inclusion Criteria

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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

<24 hours

Treatment

Participants receive either bevacizumab or placebo starting on Day 1 through discharge from the hospital

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment through the end of study

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab

Trial Overview The study compares two groups: one receiving bevacizumab and the other a placebo, in a randomized, double-blinded setup to ensure neither the participants nor the researchers know who gets which treatment until after the results are collected.

How Is the Trial Designed?

Group I: Cohort C: bevacizumab Experimental Treatment 1 Intervention

Group II: Cohort C: placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

PPD DEVELOPMENT, LP

Lead Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD Development, LP

Lead Sponsor

Biomedical Advanced Research and Development Authority

Collaborator

Trials

108

Recruited

574,000+

Edesa Biotech Inc.

Industry Sponsor

Trials

6

Recruited

2,100+

Biomedical Advanced Research and Development Authority BARDA (Funder)

Collaborator

Trials

4

Recruited

1,200+

InflaRx GmbH

Industry Sponsor

Trials

16

Recruited

2,300+

Founded

2007

Headquarters

Jena, Germany

Known For

Inflammation research

Top Products

Gohibic (vilobelimab)

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In human lung tissue, both VEGFR1 and VEGFR2 showed significant up-regulation in later stages of acute respiratory distress syndrome (ARDS), suggesting their potential role in lung injury recovery.

Neuropilin-1 (NRP-1) was down-regulated in early ARDS but normalized in later stages, indicating a complex temporal regulation of VEGF bioactivity that may contribute to the protective mechanisms in lung injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor receptor and coreceptor expression in human acute respiratory distress syndrome. Medford, AR., Ibrahim, NB., Millar, AB.[2023]

In a study using 80 male BALB/c mice, it was found that inhaling lipopolysaccharide (LPS) increased levels of vascular endothelial growth factor (VEGF), which is linked to lung injury in acute respiratory distress syndrome (ARDS).

Treatment with anti-VEGF using soluble fms-like tyrosine kinase-1 (sFlt-1) effectively reduced lung injury and helped maintain the normal structure and function of the respiratory membrane, suggesting it could be a promising therapeutic approach for ARDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor increased the permeability of respiratory barrier in acute respiratory distress syndrome model in mice. Zhang, Z., Wu, Z., Xu, Y., et al.[2022]

In a randomized trial involving 49 adults with COVID-19-associated ARDS, the drug FX06 did not significantly reduce vascular leakage compared to placebo, as measured by the extravascular lung-water index over 7 days.

While adverse event rates were similar between the FX06 and placebo groups, a higher incidence of ventilator-associated pneumonia was observed in the FX06 group, suggesting potential safety concerns that need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial. Guérin, E., Belin, L., Franchineau, G., et al.[2023]

Bevacizumab, when combined with chemotherapy, significantly improves clinical outcomes and delays disease progression in patients with advanced non-squamous non-small-cell lung cancer (NSCLC), as demonstrated in pivotal phase III trials involving large patient populations.

The safety profile of bevacizumab is well-characterized, with manageable adverse events such as hypertension and bleeding, and the overall incidence of serious side effects is similar to that of placebo, indicating it can be safely administered in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging safety data for bevacizumab in advanced non-small-cell lung cancer. Hirsh, V.[2015]

Bevacizumab, an antibody targeting VEGF, is effective for treating various cancers, including metastatic colon cancer and non-small-cell lung cancer, but it carries significant risks of severe side effects such as arterial thromboembolism and stroke.

The report highlights two fatal cases of arterial thromboembolic events in cancer patients treated with bevacizumab, emphasizing the need for careful monitoring and documentation of adverse effects associated with antiangiogenic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implication of bevacizumab in fatal arterial thromboembolic incidents. Grivas, AA., Trafalis, DT., Athanassiou, AE.[2015]

Vascular endothelial growth factor (VEGF) is a key player in the development of acute respiratory distress syndrome (ARDS) due to its role in increasing vascular permeability and disrupting the integrity of the alveolar capillary membrane.

Understanding VEGF biology could provide insights into its potential role in both maintaining normal lung function and contributing to lung injury, highlighting its importance in ARDS pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular endothelial growth factor in acute lung injury and acute respiratory distress syndrome. Barratt, S., Medford, AR., Millar, AB.[2020]

A comprehensive analysis of 96,477 adverse event reports related to bevacizumab revealed 2,847 cases of hemorrhage, highlighting significant safety concerns associated with its use in treating advanced malignant tumors.

The study identified 37 specific hemorrhagic signals linked to bevacizumab, particularly affecting the vascular, gastrointestinal, and nervous systems, with colorectal, lung, and breast cancers being the most commonly associated malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacovigilance study of adverse event profiles and haemorrhagic safety of bevacizumab based on the FAERS database. Tang, L., Ding, C., Li, H., et al.[2023]

Bevacizumab, an angiogenesis inhibitor, is associated with serious and potentially life-threatening toxicities, including hemorrhage, gastrointestinal perforation, and hypertension, necessitating early recognition and management.

Patients with preexisting conditions such as hypertension or cardiovascular disease are at higher risk for these toxicities, highlighting the need for careful monitoring and tailored management strategies in oncology practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intricacies of bevacizumab-induced toxicities and their management. Gressett, SM., Shah, SR.[2022]

In an in vitro study using A549 lung cells, exposure to acid significantly suppressed cell proliferation and VEGF production for at least 48 hours, indicating that acid can harm lung cells.

The addition of exogenous VEGF restored cell proliferation, and this effect was blocked by anti-VEGF antibodies, suggesting that VEGF plays a protective role in lung cell recovery after acid injury by interacting with its receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells. Ohwada, A., Yoshioka, Y., Iwabuchi, K., et al.[2020]

Bevacizumab therapy is associated with several adverse events, the most common being hypertension, which requires regular monitoring and management with antihypertensive medications during treatment.

Close monitoring for other serious complications, such as proteinuria and thromboembolic events, is crucial, as timely management can help prevent severe outcomes and improve patient safety throughout the course of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding and managing the possible adverse effects associated with bevacizumab. Shord, SS., Bressler, LR., Tierney, LA., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7864918/

Efficacy and tolerability of bevacizumab in patients with severe ... Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06701656

UCSF Acute Respiratory Distress Syndrome Trial → JUST ... This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics ...

3. trial.medpath.com trial.medpath.com/clinical-trial/2b5cfea60bb1cdbf/nct01314066-efficacy-bevacizumab-preventing-ards

Efficacy of Bevacizumab in Preventing Acute Respiratory ... This study aims to test the effectiveness of a single intravenous (IV, through the vein) dose of the study drug, bevacizumab (Avastin), in preventing/reducing ...

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04954014?term=bevacizumab&cond=Covid19&draw=2&rank=5

Pilot Study of Single Dose Bevacizumab as Treatment for ... Our hypothesis is that treating ARDS caused by COVID-19 with bevacizumab improves mortality. This is a phase II, multi-centered, randomized, open label, two- ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7352097/

Emerging pharmacological therapies for ARDS: COVID-19 ... The lack of effective ARDS therapies has been further highlighted in the evolving COVID-19 pandemic, which causes severe acute respiratory failure and ARDS in 3 ...

6. trialx.com trialx.com/clinical-trials/listings/308842/just-breathe-breathing-life-into-innovative-therapies-for-ards-cohort-c-bevacizumab/

JUST BREATHE, Breathing Life Into Innovative Therapies for ... Outcome data will be assembled for each patient over time (such as ventilatory status, oxygenation, and survival). Functional status using the WHO Ordinal scale ...