What side effects are associated with this type of intervention?

Common treatments for ARDS, such as mechanical ventilation and pharmacotherapy, can have various side effects. Mechanical ventilation may lead to ventilator-associated lung injury, infections, and barotrauma. Pharmacotherapies like glucocorticoids can cause hyperglycemia, increased risk of infection, and muscle weakness. Treatments involving mesenchymal stem cells (MSCs) and their extracellular vesicles, like ExoFlo, are still under investigation, but potential side effects may include immune reactions and thromboembolic events. Further clinical trials are needed to fully understand the safety profile of MSC-derived therapies.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for Acute Respiratory Distress Syndrome (ARDS) that involve extracellular vesicles derived from bone marrow mesenchymal stem cells, such as ExoFlo. While various investigational therapies, including stem cell-based treatments, are being studied for their potential benefits in ARDS, none have yet received FDA approval. Current ARDS management primarily focuses on supportive care, including mechanical ventilation and prone positioning, rather than specific pharmacologic or biologic treatments.

What other types of research exist?

Promising novel alternatives to ExoFlo for ARDS treatment in 2024 include normothermic ex-vivo lung perfusion (EVLP) and various pharmacologic agents such as prostaglandin E2, inhaled carbon monoxide, and oxygen free radical scavengers. These therapies are currently under investigation and show potential in improving lung function and reducing injury.

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Extracellular Vesicles

Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome

Phase 3

Recruiting

Led By Vikram Sengupta, MD

Research Sponsored by Direct Biologics, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Presence of moderate to severe ARDS as defined by the Berlin Criteria within 24 hours of the first infusion, including specific criteria related to onset, lung opacities, P/F ratio, ventilation, and respiratory failure

Be older than 18 years old

Must not have

Stated unwillingness to comply with all study procedures and availability for the duration of the study

Major physical trauma in the last 2 days, including motor vehicle accidents, assaults, mechanical falls with sequelae of significant bleeding or craniofacial bruising, and surgeries, such that not one or more injury may be undiagnosed at time of screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 61 days

Awards & highlights

Pivotal Trial

Summary

This trial tests a new treatment where tiny particles from bone marrow cells are used to help patients with severe lung problems by reducing inflammation and repairing lung damage.

Who is the study for?

This trial is for adults aged 18-75 with moderate-to-severe ARDS, as defined by the Berlin Criteria, and who have been on a ventilator for less than 3 days. Excluded are those with certain liver enzyme levels, severe disabilities, pregnant women, recent investigational drug use, active malignancy requiring treatment (except skin cancer), unwillingness to follow study procedures or use effective birth control.

What is being tested?

The EXTINGUISH ARDS trial tests the safety and effectiveness of ExoFlo—an IV therapy using extracellular vesicles from bone marrow stem cells—against a saline placebo in hospitalized patients with moderate-to-severe ARDS to see if it can improve their lung function.

What are the potential side effects?

While specific side effects of ExoFlo are not listed here, potential risks may include reactions at the infusion site, immune responses to foreign substances in the body, or complications related to underlying conditions worsened by additional treatments.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with severe lung distress recently.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am willing and able to follow all study procedures for its duration.

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I have not experienced major physical trauma or injuries in the last 2 days.

Select...

I have been diagnosed with cirrhosis.

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I am unwilling to use two effective birth control methods or remain abstinent.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 61 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~61 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 61 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Evaluation of 60-day All-cause Mortality

Secondary study objectives

ICU free days

Incidence of Treatment Emergent Serious Adverse Events (TESAEs)

Oxygen free days

+2 more

Side effects data

From 2021 Phase 2 trial • 102 Patients • NCT04493242

35%

Acute Respiratory Failure

26%

Anxiety

24%

Hypotension

24%

Hypokalaemia

15%

Respiratory Failure

12%

Cardiac Arrest

12%

Hyperkalaemia

Anaemia

Leukocytosis

Hyperglycaemia

Constipation

Pyrexia

Agitation

Pneumonia

Embolism

Hypertension

Multiple Organ Dysfunction Syndrome

Sepsis

Hypoalbuminaemia

Thrombocytopenia

Atrial Fibrillation

Type 2 Diabetes Mellitus

Fluid Overload

Hypophosphataemia

Upper Respiratory Tract Infection

Myalgia

Confusional State

Acute Kidney Injury

Hypothermia

Septic Shock

Dyspepsia

Cough

Nasal Congestion

Rales

Fungal Skin Infection

Bradycardia

Pancreatitis

Musculoskeletal Chest Pain

Encephalopathy

Renal Ischemia

Renal Tubular Necrosis

Pneumothorax

Atrial Flutter

Myocardial Ischaemia

Tachycardia

Blood Glucose Increased

Diabetes Mellitus

Abdominal Pain

Diarrhoea

Nausea

Oropharyngeal Pain

Pharyngeal Haemorrhage

Fall

Hypocalcaemia

Oedema Peripheral

Fungaemia

Wound Infection

Hypernatraemia

Hyperphosphataemia

Malnutrition

Syncope

Acidosis

Troponin I Increased

Dehydration

Epistaxis

Enterococcal Infection

100%

80%

60%

40%

20%

Study treatment Arm

Experimental Dose 1

Placebo

Experimental Dose 2

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Experimental DoseExperimental Treatment1 Intervention

Normal saline 85 mL and ExoFlo 15 mL

Group II: PlaceboPlacebo Group1 Intervention

Normal saline 100 mL

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ExoFlo

2020

Completed Phase 2

~110

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) are being investigated for their potential to treat Acute Respiratory Distress Syndrome (ARDS). These EVs contain proteins, microRNAs, and other molecules that can modulate immune responses, reduce inflammation, and promote lung tissue repair. Specifically, they help in reducing pulmonary vascular leakage, facilitating the repair of the pulmonary epithelium, and attenuating acute lung injury. This is crucial for ARDS patients as it addresses the underlying inflammation and tissue damage that characterize the syndrome, potentially improving outcomes and reducing mortality. Other common treatments for ARDS include systemic glucocorticoids to reduce inflammation and supportive care like mechanical ventilation to maintain adequate oxygenation.

MiR-223-3p-loaded exosomes from bronchoalveolar lavage fluid promote alveolar macrophage autophagy and reduce acute lung injury by inhibiting the expression of STK39.Differential Lung Protective Capacity of Exosomes Derived from Human Adipose Tissue, Bone Marrow, and Umbilical Cord Mesenchymal Stem Cells in Sepsis-Induced Acute Lung Injury.Exosomes Derived From Alveolar Epithelial Cells Promote Alveolar Macrophage Activation Mediated by miR-92a-3p in Sepsis-Induced Acute Lung Injury.