Oxygen and Bi-Level Ventilation for Overlap Syndrome

(CRESCENDO-SLP Trial)

Overseen By Pamela DeYoung, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must not be taking: Breathing medications, Hormones

Disqualifiers: Premenopausal, Cardiac devices, Severe sleep disorders, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different nighttime treatments affect heart health in individuals with overlap syndrome, a condition involving both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). The study compares bi-level positive airway pressure (PAP) therapy and oxygen therapy to determine which better supports cardiovascular health. It targets those with untreated moderate to severe OSA or COPD who are not currently using oxygen or PAP therapy. Participants should also experience significant sleep-related breathing issues that impact daily life. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important advancements in heart health management.

Will I have to stop taking my current medications?

The trial requires participants to be on stable medications for COPD, as assessed by a board-certified pulmonologist. However, if you are taking medications or hormones that affect breathing, you may be excluded from the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Bi-Level Positive Airway Pressure (BiPAP) therapy is generally safe for people. It often aids those with breathing difficulties, such as individuals with sleep apnea or heart failure. Studies indicate that while most people tolerate BiPAP well, rare side effects can occur, including air getting trapped in the skull, though such cases are uncommon.

The safety of oxygen therapy depends on its usage. Oxygen therapy is common for those with breathing problems, but it carries some risks. Excessive oxygen intake might lead to oxygen toxicity, which is harmful. There is also a small risk of infection with various oxygen therapies. However, when properly monitored, oxygen therapy is usually safe.

Overall, both treatments under study have been used for other conditions, demonstrating general safety but requiring careful use to manage any rare risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Overlap Syndrome because they offer unique approaches compared to existing therapies like CPAP (Continuous Positive Airway Pressure). Bi-Level Positive Airway Pressure (BiPAP) is distinctive because it provides two different pressure levels: a higher one when you inhale and a lower one when you exhale, potentially improving comfort and compliance during sleep. Meanwhile, oxygen therapy delivers supplemental oxygen, which could enhance blood oxygen levels at night, addressing respiratory issues more directly. These innovative approaches might offer better symptom management and improved quality of life for individuals with Overlap Syndrome.

What evidence suggests that this trial's treatments could be effective for overlap syndrome?

This trial will compare the effects of two treatments for overlap syndrome. Participants in one arm will receive bi-level positive airway pressure (PAP) therapy. Research shows that this therapy can improve breathing and heart health in individuals with both COPD and OSA. Studies suggest that bi-level PAP enhances sleep quality and reduces breathing problems more effectively than some other treatments. In another arm, participants will receive oxygen therapy. Evidence indicates that oxygen therapy can increase oxygen levels during sleep, but it may not significantly reduce breathing interruptions. Overall, bi-level PAP may provide greater benefits for sleep and breathing issues than oxygen alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Atul Malhotra, MD

Principal Investigator

UCSD

Are You a Good Fit for This Trial?

This trial is for people with a BMI between 24-32 who have both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), known as Overlap Syndrome. It's not suitable for individuals outside this BMI range.

Inclusion Criteria

I have signed and dated the consent form.

BMI 20-34 kg/m2 (to allow MRI scanning and to reduce variance)

I am a woman and I am postmenopausal.

Exclusion Criteria

I am currently receiving treatment for cancer.

I have central sleep apnea or irregular breathing patterns during sleep.

I am not taking any medications that could affect my breathing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (online or via phone), 1 visit (in-person)

Baseline Assessment

Eligible participants undergo an overnight visit for general exams, questionnaires, blood tests, cardiovascular and neurocognitive assessments, and a sleep study

1 day

1 overnight visit (in-person)

Treatment

Participants with OVS are randomized to receive either bi-level PAP therapy or oxygen therapy for 6 months

6 months

Weekly calls for adherence check

Follow-up

Participants return for an overnight visit and a daytime visit for cardiac MRI to assess the effects of the treatment

1-2 days

1 overnight visit, 1 daytime visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bi-Level Positive Airway Pressure
• Oxygen gas

Trial Overview The study tests whether using bi-level positive airway pressure at night or just oxygen therapy can improve heart health in those with COPD/OSA Overlap Syndrome, compared to those with only OSA or COPD.

How Is the Trial Designed?

Group I: Oxygen Experimental Treatment 1 Intervention

OVS subjects will receive treatment with oxygen during night time for 6 months

Group II: Bi-level positive pressure non invasive ventilation Experimental Treatment 1 Intervention

OVS subjects will receive treatment with bi-level PAP therapy during night time for 6 months

Bi-Level Positive Airway Pressure is already approved in United States, European Union, Canada for the following indications:

Approved in United States as BiPAP for:

• Obstructive Sleep Apnea (OSA)
• Chronic Obstructive Pulmonary Disease (COPD)
• Overlap Syndrome

Approved in European Union as BiPAP for:

• Obstructive Sleep Apnea (OSA)
• Chronic Obstructive Pulmonary Disease (COPD)
• Overlap Syndrome

Approved in Canada as BiPAP for:

• Obstructive Sleep Apnea (OSA)
• Chronic Obstructive Pulmonary Disease (COPD)
• Overlap Syndrome

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

In a study of 21 patients with overlap syndrome and hypercapnia, Auto-trilevel PAP ventilation significantly reduced the number of apnea-hypopnea events and improved sleep quality compared to fixed BiPAP ventilation.

Auto-trilevel PAP also effectively lowered morning carbon dioxide levels and daytime sleepiness, demonstrating its superiority in managing hypercapnic overlap syndrome and enhancing overall patient comfort during sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of auto-trilevel positive airway ventilation in hypercapnic patients with overlap syndrome]. Quan, W., Ding, N., Dong, Y., et al.[2018]

In a study involving 830 patients after cardiothoracic surgery, high-flow nasal oxygen therapy was found to be as effective as BiPAP in preventing treatment failure, with similar rates of reintubation and switching treatments (21.0% vs 21.9%).

High-flow nasal oxygen therapy also resulted in fewer skin breakdown issues compared to BiPAP, suggesting it may be a more comfortable option for patients at risk of respiratory failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial. Stéphan, F., Barrucand, B., Petit, P., et al.[2022]

In a study of 58 patients with mild-to-moderate hypoxemic respiratory failure, the BiPAP·S/T-AVAPS mode did not show superior effectiveness compared to the conventional BiPAP·S/T mode in terms of success rates for noninvasive mechanical ventilation (NIMV).

Both ventilatory strategies had similar rates of intubation and mortality, with a high mortality rate of 22.4% observed among patients who experienced NIMV failure, highlighting the serious risks associated with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Mechanical Ventilation with Average Volume-Assured Pressure Support versus BiPAP S/T in De Novo Hypoxemic Respiratory Failure. Briones-Claudett, KH., Briones-Claudett, MH., Baños, MDPC., et al.[2022]

In a study of 32 hypercapnic overlap syndrome patients with moderate-to-severe obstructive sleep apnea, auto-trilevel positive airway pressure (PAP) therapy was found to be more effective than conventional Bilevel PAP therapy in reducing apnea events and carbon dioxide retention, leading to improved sleep quality.

Auto-trilevel PAP therapy resulted in lower arousal indices and daytime sleepiness, while also achieving higher minimum oxygen saturation levels during sleep, indicating it may be a better treatment option for patients who do not respond well to standard Bilevel PAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auto-trilevel versus bilevel positive airway pressure ventilation for hypercapnic overlap syndrome patients. Su, M., Huai, D., Cao, J., et al.[2019]

In a study of 120 adult patients undergoing surgery with cardiopulmonary bypass, bilevel positive airway pressure (BiPAP) was applied to 31 patients with low oxygen levels after extubation, significantly improving their oxygenation levels (PaO2/FiO2 increased from 128 to 198).

BiPAP therapy allowed patients with initially poor oxygenation to achieve oxygen levels comparable to those of patients who did not require this intervention, demonstrating its efficacy as a non-invasive support method for lung function post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effects of bilevel positive airway pressure after surgery under cardiopulmonary bypass. Takami, Y., Ina, H.[2007]

Noninvasive positive pressure ventilation using BiPAP effectively improved respiratory function in three patients experiencing respiratory insufficiency and hypoxemia in the postanesthesia care unit.

BiPAP treatment led to a decrease in respiratory rate and PaCO2 levels, as well as improved oxygenation, demonstrating its efficacy in managing respiratory issues after anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive ventilation using bilevel positive airway pressure to treat impending respiratory failure in the postanesthesia care unit. Tobias, JD.[2019]

In a study of 18 patients with acute exacerbation of COPD, Bi-level Positive Airway Pressure (Bi-pap) significantly improved respiratory and heart rates, with respiratory rates decreasing from 33.2 to 22.0 breaths per minute and heart rates from 113.2 to 90.2 beats per minute (both P < 0.001).

Bi-pap also improved blood gas levels, decreasing carbon dioxide (PaCO2) from 76.5 to 51.3 mmHg and increasing oxygen levels (PaO2) from 52.1 to 62.9 mmHg, demonstrating its efficacy in managing acute respiratory failure in COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Bi-pap in acute respiratory failure due to acute exacerbation of COPD. Rizvi, N., Mehmood, N., Hussain, N.[2008]

Bilevel positive airway pressure (BiPAP) significantly improved ventilation and vital signs more rapidly than continuous positive airway pressure (CPAP) in patients with acute pulmonary edema, as shown by reductions in breathing frequency, heart rate, blood pressure, and carbon dioxide levels after just 30 minutes.

However, the use of BiPAP was associated with a higher rate of myocardial infarctions (71%) compared to CPAP (31%), indicating a potential safety concern that warrants further investigation into its hemodynamic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Mehta, S., Jay, GD., Woolard, RH., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11388228/

Prognostic efficacy of non-invasive ventilation in patients with ... Patients with overlap syndrome (OS) exhibit ventilatory defects in both lower and upper airway and experience more adverse outcomes, including ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05237505

The Cardiovascular Consequences of Sleep Apnea Plus ... Researchers will compare the effects of bi-level PAP on cardiovascular health with the effects of oxygen to see if bi-level may be an effective treatment for ...

3. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.9506

A pilot randomized trial comparing CPAP vs bilevel PAP ... Study Impact: The current study suggests bilevel positive airway pressure therapy (spontaneous mode) is superior to continuous positive airway pressure therapy ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03766542/continuous-positive-pressure-versus-bi-level-in-overlap-syndrome

Continuous Positive Pressure Versus Bi-level in Overlap ... Treatment with continuous positive airway pressure (CPAP) has been showed to be effective and associated with improved survival and decreased ...

5. journals.lww.com journals.lww.com/ecdt/fulltext/2021/70030/assessment_of_different_positive_airway_pressure.6.aspx

Assessment of different positive airway pressure... Statistically significant improvement was observed regarding sleep parameters (apnea/hypopnea index, oxygen desaturation index, and snoring index) and ABG ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03766542

Continuous Positive Pressure Versus Bi-level in Overlap ... Positive airway pressure will be applied in the experimental group through a oronasal interface, in ventilatory support mode (Bi-level) with a fixed backup rate ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4244615/

Positive airway pressure therapy for heart failure - PMC Bi-level PAP with S-mode can be used for patients who require high-pressure CPAP to control OSA or for those who cannot tolerate exhaling against high pressure ...

8. withpower.com withpower.com/trial/phase-syndrome-11-2020-cd119

Positive Airway Pressure Therapy for Overlap Syndrome Positive Airway Pressure Therapy, including CPAP and BiPAP, is generally considered safe for humans. However, rare complications like pneumocephalus (air ...

9. hopkinsmedicine.org hopkinsmedicine.org/health/treatment-tests-and-therapies/bipap

BiPap What is BiPap? Some health problems can make it hard for you to breathe. In these cases, you might get help from bilevel positive airway pressure.

10. sleepfoundation.org sleepfoundation.org/cpap/cpap-vs-bipap

BiPAP vs. CPAP Machines: Breaking Down the Differences Bilevel positive airway pressure machines have distinct air pressure settings for inhalation (IPAP) and exhalation (EPAP). The EPAP setting is ...