Positive Airway Pressure for Stroke Recovery

(RISE-UP Trial)

Overseen By Radu Radulescu, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Disqualifiers: Past PAP use, Other sleep disorders, Life expectancy < 6 months, Mechanical ventilation, Non-English speakers, Central sleep apnea, Resting oxygen saturation < 90%, Inability to consent, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether positive airway pressure (PAP) treatment can improve recovery from acute ischemic stroke in individuals with moderate to severe obstructive sleep apnea (OSA). The study compares the recovery of those using PAP therapy with those receiving usual care, which includes education on healthy lifestyles. Individuals who have experienced a stroke within the last few days and have diagnosed moderate to severe sleep apnea might be suitable candidates.

As an unphased trial, this study provides a unique opportunity to contribute to understanding the potential benefits of PAP therapy in stroke 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 prior data suggests that this PAP treatment is safe for stroke recovery?

Research has shown that Positive Airway Pressure (PAP) therapy is generally safe, even for individuals who have experienced a stroke. Studies indicate that PAP can aid stroke recovery by enhancing movement skills and reducing the risk of further blood vessel issues. Most individuals tolerate the treatment well. However, minor side effects may occur, such as discomfort from wearing the mask or air leaks. Guidance and support are crucial when beginning PAP therapy to address any concerns. Overall, evidence suggests that PAP is a promising and safe option for aiding stroke recovery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Positive Airway Pressure (PAP) for stroke recovery because it offers a novel approach by addressing sleep apnea, which is often overlooked in stroke treatment. Unlike standard stroke care, which typically focuses on medication and physical therapy, PAP aims to improve oxygen flow and brain recovery by ensuring better sleep quality. This method could enhance recovery outcomes and reduce secondary stroke risks, providing a fresh angle that complements existing stroke management strategies.

What evidence suggests that this trial's treatments could be effective for stroke recovery?

Studies have shown that Positive Airway Pressure (PAP) can aid stroke patients in more effective recovery. In this trial, some participants will receive PAP treatment either in the acute phase, starting within one week post-stroke, or in the subacute phase, starting one month post-stroke. Research indicates that PAP treatment for those with sleep apnea enhances movement and daily function after a stroke. A review of several studies found PAP to be both practical and beneficial for stroke patients with sleep apnea. Patients can use PAP easily, and it aids in their recovery after a stroke. Generally, PAP is a safe and effective treatment for sleep apnea, which is common in stroke patients. Overall, PAP shows promise in helping stroke patients with sleep apnea recover. ^{1 4 5 6 7}

Who Is on the Research Team?

Klar Yaggi, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

National Institute of Nursing Research (NINR)

Collaborator

Trials

623

Recruited

10,400,000+

American Academy of Sleep Medicine Foundation (AASM)

Collaborator

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4918984/

Effect of Continuous Positive Airway Pressure on Stroke ... Treatment with continuous positive airway pressure (CPAP) among patients diagnosed with OSA is associated with improved functional and motor outcome after ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10476038/

Effectiveness and feasibility of continuous positive airway ... This meta-analysis aimed to investigate the feasibility and effectiveness of continuous positive airway pressure (CPAP) treatment in stroke patients with sleep ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00368628

Continuous Positive Airway Pressure for the Treatment of ... Among patients without stroke, continuous positive airway pressure (CPAP) is a safe and effective treatment for sleep apnea. This feasibility pilot study is a ...

4. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.120.031709

Trials in Sleep Apnea and Stroke Few randomized controlled trials have evaluated the effectiveness of continuous positive airway pressure (CPAP) in reducing recurrent vascular events and ...

5. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1624631/abstract

Continuous positive airway pressure in acute ischemic ... This study aimed to assess the impact of CPAP on hospitalization outcomes for AIS-OSA patients using data from the National Inpatient Sample (NIS). Methods A ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10032615/

Positive airway pressure therapy for post-stroke sleep ... Conclusions. PAP therapy was effective in reducing recurrent vascular events. The beneficial effects were also observed in other health outcomes ...

7. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.10680

Effectiveness and feasibility of continuous positive airway ... The current analysis found that CPAP therapy in patients with stroke and SA provides a beneficial effect on neurological recovery, consistent with the results ...