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

Trial Summary

What is the purpose of this trial?

Major progress has been made in the area of cardiovascular disease, but we believe that further progress will involve mechanistically addressing underlying respiratory causes including chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). The most common cause of death in COPD is cardiovascular, although mechanisms are unknown. OSA has been associated with major neurocognitive and cardiovascular sequelae, the latter likely a function of autonomic nervous system abnormalities, oxidative stress, inflammation, and other pathways. Recent data suggest that individuals with OVS die preferentially of cardiovascular disease compared to OSA or COPD alone, although mechanisms are again unclear. The combination of OSA and COPD may lead to profound hypoxemia. Individuals with COPD can develop pulmonary hypertension via disturbances in gas exchange and parenchymal injury leading to loss of pulmonary vasculature. OSA has been associated with mild to moderate pulmonary hypertension, but the situation may be worse if combined with parenchymal lung disease. The biological response to sustained hypoxemia has been carefully studied as has the topic of intermittent hypoxemia; however, to our knowledge, very little research has occurred regarding the combination of sustained plus intermittent hypoxia as seen in OVS. For example, we do not really know whether individuals with OVS develop coronary disease, right or left heart failure, dysrhythmias or some combination of abnormalities predisposing them to cardiovascular death. Thus, design of interventional studies is challenging as causal pathways are poorly understood despite our considerable preliminary data addressing these issues. The purpose of this study is to examine vascular mechanisms in individuals with COPD/OSA overlap syndrome (OVS) compared with matched individuals with obstructive sleep apnea (OSA) alone or chronic obstructive pulmonary disease (COPD) alone and to perform a phase II pilot mechanistic clinical trial in OVS to examine the effect size of nocturnal bi-level positive airway pressure (PAP) vs. nocturnal oxygen therapy in cardiovascular outcomes.

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.

What data supports the effectiveness of the treatment Bi-Level Positive Airway Pressure (BiPAP) and Oxygen therapy for Overlap Syndrome?

Research shows that Bi-Level Positive Airway Pressure (BiPAP) therapy can improve breathing in patients with acute respiratory failure and enhance oxygenation after surgery. This suggests it may help manage breathing issues in Overlap Syndrome by improving lung function and oxygen levels. ^{1 2 3 4 5}

How does the treatment of Bi-Level Positive Airway Pressure and Oxygen differ for overlap syndrome?

This treatment combines Bi-Level Positive Airway Pressure (BiPAP), which helps keep the airways open by providing two levels of air pressure, with oxygen therapy to improve breathing in patients with overlap syndrome. It is unique because it addresses both airway obstruction and low oxygen levels, unlike some other treatments that may not effectively manage both issues simultaneously. ^{2 5 6 7 8}

Research Team

Atul Malhotra, MD

Principal Investigator

UCSD

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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 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]

References

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

Beneficial effects of bilevel positive airway pressure after surgery under cardiopulmonary bypass. [2007]

2. Germany pubmed.ncbi.nlm.nih.gov

Auto-trilevel versus bilevel positive airway pressure ventilation for hypercapnic overlap syndrome patients. [2019]

3. Pakistan pubmed.ncbi.nlm.nih.gov

Role of Bi-pap in acute respiratory failure due to acute exacerbation of COPD. [2008]

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

Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. [2023]

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

High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Efficacy of auto-trilevel positive airway ventilation in hypercapnic patients with overlap syndrome]. [2018]

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

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

8. Egypt pubmed.ncbi.nlm.nih.gov

Noninvasive Mechanical Ventilation with Average Volume-Assured Pressure Support versus BiPAP S/T in De Novo Hypoxemic Respiratory Failure. [2022]