Neuromuscular Blockade for Acute Respiratory Distress Syndrome

(PNEUMA Trial)

Overseen By Jenna Wong, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: Neuromuscular blockers

Disqualifiers: Decannulation, Esophageal contraindication, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 hours

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of using neuromuscular blockade (NMB) for individuals with severe acute respiratory distress syndrome (ARDS) who require a special type of life support called VV-ECMO. The researchers aim to determine if adjusting the treatment to permit some natural breathing is safe and feasible. Suitable candidates are those currently receiving neuromuscular blockade due to ARDS and needing VV-ECMO support to breathe. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance future treatment options for ARDS patients.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications. However, it seems that participants need to be on neuromuscular blockade medication, as the trial involves adjusting this treatment.

What prior data suggests that this novel approach to neuromuscular blockade is safe for patients with severe ARDS?

Research has shown that treatments called neuromuscular blockade (NMB) can be safe for patients with acute respiratory distress syndrome (ARDS). One large study demonstrated that using continuous NMB for the first 48 hours in the ICU improved survival rates for patients with severe ARDS. This suggests that NMB can aid in their recovery.

Another study found that NMB can ease breathing for patients on ventilators by reducing muscle movement, which helps keep their lungs clear of fluid.

Overall, these studies suggest that NMB is a well-tolerated option for people with severe breathing problems in the ICU. While discussing any concerns with healthcare providers is important, current research indicates that NMB is safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Neuromuscular blockade is unique because it offers a different approach to managing Acute Respiratory Distress Syndrome (ARDS). Unlike standard treatments that primarily focus on improving oxygenation and reducing inflammation, such as mechanical ventilation and corticosteroids, neuromuscular blockade aims to reduce the work of breathing and improve ventilation by temporarily paralyzing the muscles involved in breathing. This can potentially decrease lung injury caused by the mechanical ventilator itself. Researchers are excited about this treatment because it could lead to more effective management of ARDS, reducing complications and improving outcomes for patients.

What evidence suggests that neuromuscular blockade might be an effective treatment for acute respiratory distress syndrome?

Research has shown that a treatment called neuromuscular blockade (NMB) can aid individuals with acute respiratory distress syndrome (ARDS). One large study found that continuous NMB use for the first 48 hours in the intensive care unit extended the lives of patients with severe ARDS over a 90-day period. Another study demonstrated that NMB improves oxygen levels in patients with moderate to severe ARDS after 48 hours and reduces the risk of lung injury. NMB also eases breathing by reducing the struggle with ventilators and preventing fluid buildup in the lungs. Overall, NMB shows promise in improving outcomes for ARDS patients. Participants in this trial will receive a partial NMB treatment to further evaluate its effectiveness. ^{1 2 3 5 6}

Who Is on the Research Team?

Ewan Goligher, MD, PhD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for patients with severe ARDS who are on ECMO support and show potentially harmful respiratory efforts. They must be deeply sedated or require neuromuscular blockade to tolerate ECMO, as decided by their medical team. Patients already receiving neuromuscular blockers without plans to stop before the next day can also join.

Inclusion Criteria

I have severe breathing issues and am deeply sedated.

My team tried stopping muscle relaxants but decided I need them for my ECMO treatment.

I am on muscle relaxants with plans to continue until at least tomorrow.

Exclusion Criteria

Contraindication to esophageal catheterization

Contraindication to neuromuscular blockade (allergy, history of malignant hyperthermia)

I am expected to be taken off ECMO support within 24 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive partial neuromuscular blockade to maintain safe spontaneous breathing in ARDS patients on VV-ECMO

24 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Neuromuscular Blockade

Trial Overview The PNEUMA trial is testing a new method of adjusting neuromuscular blockers to allow safe spontaneous breathing in patients with severe ARDS on veno-venous ECMO. It's an early-stage trial focusing on safety and how well this approach works.

How Is the Trial Designed?

Group I: Partial NMB Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10919110/

A Mechanism May Be Prevention of Expiratory Muscle Activity ... One large trial found that continuous neuromuscular block for the first 48 hours of the ICU stay improved 90-day mortality in patients with severe ARDS.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6986163/

Neuromuscular blockade in acute respiratory distress ... NMBA improves oxygenation only after 48 h in moderate, severe ARDS patients and has a lower barotrauma risk without affecting ICU weakness.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1901686

Early Neuromuscular Blockade in the Acute Respiratory ... For example, neuromuscular blockade reduces patient–ventilator dyssynchrony, the work of breathing, and the accumulation of alveolar fluid; ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0147956322002369

The use of early neuromuscular blockage in acute ... Neuromuscular blockers compared to any comparator in treating ARDS showed a reduction in mortality (RR 0.79 [95% CI, 0.62 to 0.99]). No difference in ventilator ...

5. icm-experimental.springeropen.com icm-experimental.springeropen.com/articles/10.1186/s40635-020-00348-6

Neuromuscular blocking agents in acute respiratory distress ... Previous trials showed that a continuous NMBA infusion for 48 h improves survival in patients with moderate to severe ARDS [8]. The mechanism of ...

6. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-020-2765-2

Validation of neuromuscular blocking agent use in acute ... The use of NMBAs could significantly decrease mortality in moderate-to-severe ARDS patients and decrease the incidence of barotrauma during mechanical ...