Breakthrough Clinical Results
ClearFlow, Inc. announced positive clinical trial results showing that its PleuraFlow Active Clearance Technology (ACT) System significantly improves outcomes in cardiac surgery when integrated into an Enhanced Recovery After Surgery (ERAS) program. The prospective study, conducted at Franciscan Health Indianapolis, involved 1,334 adult patients and demonstrated a 41% reduction in retained blood syndrome (RBS), a 17% decrease in postoperative atrial fibrillation (POAF), a 30% reduction in median ICU hours, and a 64% reduction in ICU readmissions in the group using the PleuraFlow system compared to a control group. The system maintains chest tube patency, reducing retained blood and associated complications. These findings support the system's role in enhancing patient recovery and aligning with ERAS Cardiac Society recommendations.
Key Highlights
- 41% reduction in retained blood syndrome (RBS)
- 17% decrease in postoperative atrial fibrillation (POAF)
- 30% reduction in median ICU hours
- 64% reduction in ICU readmissions
Study Design Parameters
Several articles discuss the design and endpoints of clinical trials in cardiac surgery, highlighting key considerations and challenges.
Study Design Parameters:
- Patient Selection: Studies emphasize careful consideration of patient selection to ensure a representative cohort and clinical equipoise. The SYNTAX trial, for instance, uses a "Heart Team" approach for patient selection, allocating eligible patients with 3-vessel or left main disease to either PCI or CABG based on whether comparable revascularization can be achieved by both methods. Trials often employ restrictive inclusion criteria, as seen in the majority of positive RCTs in acute ischemic stroke treatment. Some trials, like TRICS III, randomize patients before surgery to capture the most acute hemoglobin reduction during cardiopulmonary bypass. However, underrepresentation of women in cardiac surgery RCTs is a concern, with a decreasing proportion observed over time.
- Intervention and Control Groups: Clear definition of treatment and control groups is crucial. The DECS-II trial compares high-dose dexamethasone with placebo in cardiac surgery patients. The AdaptResponse trial compares adaptive left ventricular-only pacing with conventional cardiac resynchronization therapy. The BRIDGE trial evaluated cangrelor as a bridge to CABG in patients on extended dual antiplatelet therapy. The ALBICS study investigates the impact of postoperative albumin infusion on kidney function after high-risk cardiac surgery.
- Randomization and Blinding: Randomization and blinding are essential for minimizing bias. The PRECORE study used Best-Worst Scaling to elicit patient preferences for component endpoints, highlighting the importance of patient perspectives in endpoint selection. Blinding can be challenging in surgical trials, but efforts should be made to blind outcome assessors whenever possible. TRICS III, for example, is an open-label trial but monitors adherence to transfusion triggers closely.
- Sample Size and Power: Sample size calculations are crucial for ensuring adequate power to detect meaningful differences. Many trials include fewer than 1000 patients, but highly selective inclusion criteria can enhance the ability to identify efficacy in specific subgroups. The TRICS III trial enrolled 5000 patients to compare restrictive and liberal transfusion strategies.
- Follow-up Duration: Adequate follow-up duration is necessary to capture relevant outcomes. The SYNTAX trial uses a primary endpoint of major adverse cardiac and cerebral events at 1 year. The BioPace trial follows pacemaker patients for up to 5 years to assess survival, quality of life, and functional capacity. The SOS study followed obese subjects for up to 20 years to evaluate the long-term effects of bariatric surgery.
- Data Collection and Reporting: Standardized data collection and reporting are essential for facilitating comparisons across trials. The Standardized Data Collection for Cardiovascular Trials Initiative has developed uniform definitions for cardiovascular and stroke outcomes. Heterogeneity in outcome reporting remains a challenge, and efforts are underway to develop core outcome sets for cardiac surgery trials.
Endpoints:
- Mortality and Morbidity: Mortality (all-cause and cardiovascular) is a common endpoint in cardiac surgery trials. Other major adverse events, such as myocardial infarction, stroke, and renal dysfunction, are also frequently assessed. The HOPE study used a composite endpoint of cardiovascular death, non-fatal MI, and non-fatal stroke. The TRICS III trial used a composite of mortality, MI, stroke, and new-onset renal dysfunction.
- Functional Capacity and Quality of Life: Functional capacity and quality of life are important patient-centered outcomes. The BioPace trial assesses quality of life and 6-minute hall walk distance. The KCCQ is used to measure health status in heart failure trials, such as DAPA-HF and DELIVER. The EFFECT study evaluates quality of life and fatigue in patients with metastatic breast cancer undergoing cardiac surgery.
- Surrogate Endpoints: Surrogate endpoints, such as biomarkers and imaging parameters, are sometimes used in cardiac surgery trials. The TRIBE-AKI study investigated biomarkers for predicting AKI after cardiac surgery. CMR is used to assess myocardial tissue characteristics in trials of cardioprotective strategies. However, validation of surrogate endpoints is crucial to ensure they reliably predict clinically meaningful outcomes.
- Composite Endpoints: Composite endpoints are frequently used in cardiovascular trials to increase statistical power, but their interpretation can be challenging. The PRECORE study examined patient preferences for different components of a composite endpoint. The Standardized Data Collection for Cardiovascular Trials Initiative has developed uniform definitions for components of composite endpoints.
Challenges and Future Directions:
Cardiac surgery trials face challenges related to patient heterogeneity, complex interventions, blinding difficulties, and slow recruitment. Standardization of outcome definitions, development of core outcome sets, and incorporation of patient-reported outcomes are important steps towards improving the quality and comparability of cardiac surgery trials. Novel trial designs, such as adaptive trials and platform trials, may also enhance efficiency and flexibility. Furthermore, the use of big data and machine learning has the potential to improve risk prediction and personalize treatment strategies in cardiac surgery.
Recent Studies
Several studies have explored interventions in cardiac surgery, focusing on enhanced recovery, prehabilitation, and alternative surgical approaches. Here's a summary of some key studies, their interventions, and safety/efficacy outcomes:
1. Enhanced Recovery After Surgery (ERAS) Protocols:
- Intervention: ERAS protocols involve a series of perioperative interventions aimed at improving patient care and outcomes. These interventions include patient education, optimized pain management, early mobilization, and minimized fasting periods.
- Efficacy Outcomes: Studies have shown significant improvements in hospital and ICU length of stay, as well as a reduction in postoperative opioid consumption. One study reported significant decreases in opioid use, nausea, and lightheadedness, along with improved functional outcomes. Another study found that ERAS protocols improved long-term patient-reported quality of life across mental health, physical health, physical functioning, and social satisfaction domains.
- Safety Outcomes: No increase in postoperative complications has been reported in studies evaluating ERAS protocols in cardiac surgery.
2. Exercise-Based Prehabilitation:
- Intervention: Exercise-based prehabilitation programs involve structured exercise and inspiratory muscle training before cardiac surgery to improve patients' physical function and reduce postoperative complications.
- Efficacy Outcomes: Studies have shown significant improvements in 6-minute walking distance both before and after surgery. Prehabilitation has also been associated with a shorter length of hospital stay and a decreased risk of postoperative atrial fibrillation in patients 65 years or younger.
- Safety Outcomes: Prehabilitation interventions have generally been well-tolerated, with no reported increase in adverse events.
3. Minimally Invasive Cardiac Surgery (MICS):
- Intervention: MICS procedures, such as MICS CABG and robotically assisted totally endoscopic CABG (TECAB), involve performing coronary artery bypass grafting through smaller incisions, avoiding sternotomy or cardiopulmonary bypass.
- Efficacy Outcomes: Studies have shown faster recovery, reduced hospitalization, and lower costs compared to conventional CABG. One study reported similar operative mortality and major morbidity rates between MICS CABG and open CABG, but MICS CABG was associated with fewer transfusions, shorter length of stay, and lower hospital costs.
- Safety Outcomes: MICS procedures have generally been shown to be safe, with comparable complication rates to conventional surgery in experienced centers.
4. Restrictive Red-Cell Transfusion Strategy:
- Intervention: A restrictive red-cell transfusion strategy involves transfusing red blood cells only when the hemoglobin concentration falls below a certain threshold (e.g., <7.5 g/dL).
- Efficacy Outcomes: Studies have shown that a restrictive strategy is noninferior to a liberal strategy with respect to the composite outcome of death, myocardial infarction, stroke, or new-onset renal failure with dialysis at both hospital discharge and 6 months after surgery.
- Safety Outcomes: No significant differences in secondary outcomes, including mortality, have been observed between restrictive and liberal transfusion strategies.
5. Remote Cardiac Rehabilitation (RCR):
- Intervention: RCR programs involve patients exercising at home using an ergometer with real-time monitoring and educational instructions provided through e-learning.
- Efficacy Outcomes: Studies have shown significant improvements in peak oxygen consumption (VO2) after RCR, comparable to the improvements seen with center-based cardiac rehabilitation.
- Safety Outcomes: RCR has been shown to be safe, with no significant cardiovascular complications reported during exercise sessions.
It's important to note that the evidence for some of these interventions is still limited, and further research, particularly large randomized controlled trials, is needed to confirm their long-term efficacy and safety.
Economic Burden
Global Access to Cardiac Surgery (2017):
- A study utilizing the Cardiothoracic Surgery Network database (August 2017) mapped global access to cardiac surgery, revealing significant disparities. North America had the highest number of cardiac surgeons per million population, with 11.12 adult and 2.08 pediatric surgeons. This contrasted sharply with sub-Saharan Africa, which had only 0.12 adult and 0.08 pediatric cardiac surgeons per million. Low-income countries had drastically lower access (0.04 adult and 0.03 pediatric surgeons per million) compared to high-income countries (7.15 adult and 1.67 pediatric surgeons per million). While the study didn't provide specific cost estimates, it highlighted the substantial gap in access, implying a significant economic burden in underserved regions.
Postoperative Atrial Fibrillation (POAF) Costs (2007):
- A prospective observational study examined the economic impact of POAF following cardiac surgery. The study found that POAF increased the average length of hospitalization by approximately 1 day, resulting in an additional cost of about 1,800 per patient. While this study focused on a specific complication of cardiac surgery, it provides insight into the potential economic burden associated with such procedures.
Economic Burden of CVD in Europe (2021):
- A more recent study (2021) estimated the broader economic burden of cardiovascular disease (CVD), including cardiac surgery, across the 27 European Union countries. The total annual cost of CVD was estimated at 282 billion, with health and long-term care accounting for 155 billion (55%). This represented 11% of total EU health expenditure. The cost per person was 630, ranging from 381 in Cyprus to 903 in Germany. Coronary heart disease and cerebrovascular diseases each accounted for 27% of the total CVD costs (77 billion and 76 billion, respectively). This study provides a more recent and comprehensive overview of the economic burden of CVD in Europe, although it doesn't isolate the specific costs of cardiac surgery.
Cardiac Surgery in LMICs (2019):
- A review of cardiac surgical care in low- and middle-income countries (LMICs) highlighted the limited access and high costs associated with these procedures. The review noted that high-income countries have over 100 times more cardiac surgeons per million population than LMICs. Globally, there are over 4,000 cardiac centers, but LMICs have less than one center per 10 million people. While the review didn't provide specific cost estimates for the USA or Europe, it emphasized the economic challenges associated with providing cardiac surgery in resource-constrained settings, indirectly suggesting the relatively higher costs in developed nations.
Summary:
While precise, recent cost estimates for cardiac surgery specifically in the USA and Europe are not readily available in the provided PubMed abstracts, the available data suggests a substantial economic burden. Factors contributing to this burden include the high cost of procedures, complications like POAF, long-term care needs, and the overall increasing prevalence of CVD. Furthermore, the disparity in access to cardiac surgery between high-income and low-income countries underscores the economic challenges associated with providing this essential care globally.
Drug used in other indications
The provided text focuses primarily on the use of the PleuraFlow Active Clearance Technology (ACT) System in cardiac surgery. While it mentions chest tubes are used in heart and lung surgery, it doesn't specifically state that the ACT system is being actively trialed for other indications beyond cardiac surgery.
However, some paragraphs hint at potential broader applications:
- Heart and Lung Surgery: One paragraph mentions chest tube clogging as a complication after "heart and lung surgery," suggesting the ACT system could be beneficial in both. The paragraph describes the system's design and function, emphasizing its ability to maintain chest tube patency, which is crucial in both heart and lung surgery. It also suggests the potential for using smaller chest tubes and less invasive insertion techniques due to the system's ability to prevent clogging. This implies a possible future application in lung surgery, though not a current active trial.
It's important to note that while these paragraphs suggest potential applications of the ACT system beyond cardiac surgery, they do not confirm active clinical trials for those indications. The focus remains firmly on cardiac surgery, with other surgical areas mentioned as potential beneficiaries of improved chest tube patency, but without specific trial details or intervention models.