Positive Airway Pressure for Stroke Recovery

(RISE-UP Trial)

Overseen By Radu Radulescu, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Up to 6 months

360 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study is a randomized controlled trial among an anicipated 180 participants with acute ischemic stroke and mod/severe OSA diagnosed by ambulatory polysomnography (PSG) comparing PAP treatment with usual care concerning the primary outcome of functional recovery.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more information.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the idea that Positive Airway Pressure for Stroke Recovery is an effective treatment?

The available research shows that Positive Airway Pressure (PAP) treatments like CPAP and BiPAP are effective in managing respiratory issues, such as acute respiratory failure and pulmonary edema. These treatments help improve breathing and reduce the need for more invasive procedures. While the studies focus on respiratory conditions, the success in these areas suggests potential benefits for stroke recovery, as improved breathing can aid overall recovery. However, specific data on stroke recovery is not provided in the available research. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Positive Airway Pressure for Stroke Recovery?

Research shows that non-invasive ventilation (NIV), including CPAP and BiPAP, is effective in improving breathing and reducing the need for more invasive procedures in patients with respiratory issues. While this is not directly related to stroke recovery, it suggests that these treatments can help improve breathing and overall health, which might support recovery in stroke patients. ^{1 2 3 4 5}

What safety data exists for positive airway pressure treatments?

The safety data for positive airway pressure treatments, such as CPAP and BiPAP, primarily comes from studies on their use in treating acute respiratory conditions. These treatments have been shown to reduce the need for invasive mechanical ventilation in conditions like acute respiratory failure and cardiogenic pulmonary edema. They are also used in infants with RSV infections and post-surgery to prevent reintubation. While these studies focus on respiratory conditions, they provide a basis for understanding the safety and effectiveness of these treatments in clinical settings. ^{1 2 3 4 6}

Is positive airway pressure treatment generally safe for humans?

Positive airway pressure treatments like CPAP and BiPAP are generally considered safe for humans and are commonly used to help with breathing problems in various conditions, such as respiratory failure and pulmonary edema. These treatments have been shown to reduce the need for more invasive procedures, like mechanical ventilation, which suggests they are a safe option for managing breathing issues. ^{1 2 3 4 6}

Is PAP a promising treatment for stroke recovery?

PAP, which includes CPAP and BiPAP, is a promising treatment because it helps people breathe better without needing invasive procedures. It has been shown to reduce the need for more serious interventions in conditions like pulmonary edema and can be effective in various settings, including before reaching the hospital. This suggests it could be beneficial for stroke recovery by improving breathing and potentially reducing complications. ^{1 2 3 4 7}

How is the Positive Airway Pressure treatment different from other stroke recovery treatments?

Positive Airway Pressure (PAP) treatment, including CPAP and BiPAP, is unique because it uses a machine to help keep the airways open by providing a steady flow of air through a mask, which is different from typical stroke recovery treatments that may focus on medication or physical therapy. This approach is commonly used for breathing issues like sleep apnea but is being explored for stroke recovery to potentially improve breathing and oxygen levels, which might aid in recovery. ^{1 2 3 4 7}

Research Team

Klar Yaggi, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults who've had an acute ischemic stroke within the past 5 days and have moderate to severe obstructive sleep apnea (OSA), confirmed by a sleep study. Participants must be able to give informed consent and not require mechanical ventilation, have other sleep disorders, or a life expectancy under 6 months.

Inclusion Criteria

I have moderate to severe sleep apnea with an AHI of 15 or higher.

My neurological symptoms started less than 5 days ago.

If you've had a recent stroke, and your brain was scanned within 48 hours of when the symptoms started.

Exclusion Criteria

You are expected to live for less than 6 months, such as if you are receiving hospice care.

I do not require mechanical ventilation to breathe.

Inability to provide their own informed consent. To enhance the generalizability of our study, all stroke severity will be included. However, we will exclude patients who cannot provide their own consent. This is because patients will need to participate actively in the protocol with a behavioral intervention. An assessment of the patient's competence to provide consent will be made based on published recommendations

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PAP treatment for OSA in ischemic stroke, starting either acutely within 1 week or subacutely within 1 month post-stroke, with ongoing technical assistance and behavioral support.

Up to 6 months

Interim contacts at 1 week, 1 month, and 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including sleep quality, pain interference, and functional recovery.

6 months

Follow-up assessments at 3 and 6 months

Exploratory

Conduct in-depth qualitative interviews with stroke patients, family members, and acute care providers to understand experiences with PAP use.

3 months

Treatment Details

Interventions

• PAP

Trial Overview The study is testing if Positive Airway Pressure (PAP) treatment improves recovery after an acute ischemic stroke compared to usual care. It's a randomized controlled trial with around 180 participants diagnosed with OSA using ambulatory polysomnography.

Participant Groups

Group I: PAP treatment- Subacute Experimental Treatment 2 Interventions

Acute intervention patients will start PAP within 1-week poststroke symptom onset, and subacute patients will start PAP 1-month post-symptom onset. Both groups will continue PAP therapy through the duration of the study, reinforced with technical assistance and behavioral support. All patients (randomized and non-randomized) will receive a healthy lifestyle education (HLE) intervention focused on secondary stroke prevention, as well as interim contacts occurring at 1 week, 1 month, and 3 months, post-randomization, where outcome measures and safety assessments will occur.

Group II: PAP treatment- Acute Experimental Treatment 2 Interventions

Acute intervention patients will start PAP within 1-week poststroke symptom onset, and subacute patients will start PAP 1-month post-symptom onset. Both groups will continue PAP therapy through the duration of the study, reinforced with technical assistance and behavioral support. All patients (randomized and non-randomized) will receive a healthy lifestyle education (HLE) intervention focused on secondary stroke prevention, as well as interim contacts occurring at 1 week, 1 month, and 3 months, post-randomization, where outcome measures and safety assessments will occur.

Group III: Exploratory arm Experimental Treatment 1 Intervention

Non-randomized comparison/exploratory group of subjects with ischemic stroke and Apnea-Hypopnea Index (AHI) \<15 (approximately 120 participants) and approximately 60 subjects with ICH (who do not need legally authorized representative for consent - most likely mild form of ICH) and any level of AHI.

Group IV: Usual Care (HLE) Active Control 1 Intervention

All patients (randomized and non-randomized) will receive a healthy lifestyle education (HLE) intervention focused on secondary stroke prevention, as well as interim contacts occurring at 1 week, 1 month, and 3 months, post-randomization, where outcome measures and safety assessments will occur.

PAP is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Sleep-disordered breathing

Approved in United States as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Sleep-disordered breathing

Approved in Canada as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Sleep-disordered breathing

Approved in Japan as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Sleep-disordered breathing

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Hartford HealthCare

Collaborator

Trials

9

Recruited

1,300+

Findings from Research

Pre-hospital continuous positive airway pressure (CPAP) significantly reduces mortality and intubation rates in adults with acute respiratory failure compared to standard care, based on a meta-analysis of 10 studies involving 650 patients.

While pre-hospital CPAP is more effective, it is also more expensive, with an incremental cost-effectiveness ratio of £20,514 per quality-adjusted life-year (QALY), indicating that its cost-effectiveness remains uncertain and warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-hospital non-invasive ventilation for acute respiratory failure: a systematic review and cost-effectiveness evaluation. Pandor, A., Thokala, P., Goodacre, S., et al.[2022]

In a study of 147 patients with pulmonary edema, early application of BiPAP (within one hour of ER admission) significantly increased the likelihood of being discharged within four hours, with 85% of early BiPAP patients discharged compared to only 15% of those who received it later.

The benefits of early BiPAP application were particularly notable in patients with congestive heart failure, where 84% were discharged within four hours compared to just 16% in the late BiPAP group, highlighting the importance of timely intervention in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of BiLevel Positive Airway Pressure (BiPAP) Application Timing on Emergency Room Length of Stay in Patients With Pulmonary Edema: A Single-Center, Retrospective Cohort Study. Khayat, S., Ali, M., Almasoudi, L., et al.[2023]

In patients with acute cardiogenic pulmonary edema, continuous positive airway pressure (CPAP) significantly reduces mortality compared to standard therapy, with a relative risk of 0.59 based on 23 trials.

Both CPAP and bilevel ventilation effectively lower the need for invasive mechanical ventilation compared to standard therapy, but no significant difference in mortality was found between CPAP and bilevel ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis. Peter, JV., Moran, JL., Phillips-Hughes, J., et al.[2023]

In a study of 254 patients undergoing cardiac or thoracic surgeries, early use of BIPAP within 48 hours after extubation improved oxygen levels (PaO2) significantly compared to later application, indicating its potential benefit in managing respiratory failure.

Despite the improvement in oxygen levels, the early use of BIPAP did not significantly reduce the reintubation rate, suggesting that while it may help with oxygenation, it does not necessarily prevent the need for reintubation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does early use of bilevel positive airway pressure (bipap) in cardiothoracic intensive care unit prevent reintubation? Sağıroğlu, G., Baysal, A., Copuroğlu, E., et al.[2020]

Non-invasive positive pressure ventilation (NIPPV) is increasingly recognized for its effectiveness in treating respiratory failure, improving gas exchange, and reducing the need for intubation, which can lead to lower mortality rates.

Recent developments and recommendations highlight the importance of proper methodology in applying NIPPV, emphasizing its role in both acute and chronic respiratory failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive ventilation in the management of respiratory failure. Chan, JK., Leung, RC., Lai, CK.[2019]

In a study of 101 infants with respiratory syncytial virus (RSV) infection, non-invasive ventilation (NIV) was successfully used as the primary respiratory support method in 68% of cases, demonstrating its feasibility in this population.

Key predictors of NIV failure included the presence of apneas, elevated admission PCO2 levels, and higher H24 PRISM scores, which can help identify infants at risk for needing more invasive support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-invasive ventilation in infants with severe infection presumably due to respiratory syncytial virus: feasibility and failure criteria]. Campion, A., Huvenne, H., Leteurtre, S., et al.[2006]

Bilevel positive airway pressure (BPAP) devices have been developed to effectively treat complex sleep-related breathing disorders that do not respond to traditional CPAP therapy, enhancing patient care for conditions like obstructive sleep apnea (OSA).

Advanced BPAP therapies, including adaptive servoventilation and volume-assured pressure support, provide tailored noninvasive ventilation options to address various hypoventilation disorders and central sleep apnea syndromes, showcasing their versatility in managing complex respiratory issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep-Related Breathing Disorders: When CPAP Is Not Enough. Selim, B., Ramar, K.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Pre-hospital non-invasive ventilation for acute respiratory failure: a systematic review and cost-effectiveness evaluation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The Impact of BiLevel Positive Airway Pressure (BiPAP) Application Timing on Emergency Room Length of Stay in Patients With Pulmonary Edema: A Single-Center, Retrospective Cohort Study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Does early use of bilevel positive airway pressure (bipap) in cardiothoracic intensive care unit prevent reintubation? [2020]

5. Australia pubmed.ncbi.nlm.nih.gov

Non-invasive ventilation in the management of respiratory failure. [2019]

6. France pubmed.ncbi.nlm.nih.gov

[Non-invasive ventilation in infants with severe infection presumably due to respiratory syncytial virus: feasibility and failure criteria]. [2006]

7. United States pubmed.ncbi.nlm.nih.gov

Sleep-Related Breathing Disorders: When CPAP Is Not Enough. [2022]