BACKGROUND:In recent years, immune checkpoint inhibitors have played a crucial role in neoadjuvant treatment of gastric cancer, but their efficacy still needs to be improved. Immunonutrition not only reduces the incidence of malnutrition but also enhances the tolerance to neoadjuvant treatment and strengthens the immune function, making it a potential immunotherapy sensitizing agent. Therefore, this study aimed to explore whether immunonutrition therapy could enhance the efficacy of gastric cancer immunotherapy by reshaping the tumor immune microenvironment, providing new ideas and schemes for the neoadjuvant therapy of locally advanced gastric cancer (LAGC). METHODS:This study is a pragmatic, open label, single-center randomised controlled study. Suitable LAGC patients were screened and randomly assigned in a 1:1 ratio to the control group - neoadjuvant chemotherapy (NAC) and the intervention group - neoadjuvant chemotherapy combined with immunotherapy and oral immunonutrition (NACII). The primary endpoint is pathological complete response after 3 cycle treatment. The following secondary endpoints will be evaluated: R0 resection rate; lymph node status after neoadjuvant therapy; The safety of the treatment plan. The accompanying changes in the immune status and tumor microenvironment is set as the exploratory endpoint. 76 LAGC at least is expected to include in this study. DISCUSSION:The present study is the first prospective trial to evaluate the effectiveness of immunocheckpoint inhibitors combined with oral immunonutrition on neoadjuvant efficacy in LAGC. This trial may provide valuable insights for enhancing immunotherapy and establish new strategies for the neoadjuvant treatment of LAGC.
INTRODUCTION:External snapping hip is a condition characterized by a painful, audible, or palpable snap during hip movement, often accompanied by physical impairments. Progressive resistance training (PRT) has shown feasibility and acceptability in this population, but its clinical and cost-effectiveness has not been evaluated in a randomized controlled trial. This protocol outlines the Snappy Hip trial, which will evaluate the effect of PRT versus no intervention on pain at 12 weeks and compare pain when PRT is initiated immediately versus after a 12-week delay. METHODS:The Snappy Hip Trial is a multicentre, randomized controlled trial. Participants aged 18-40 years with external snapping hip and symptoms within the previous 14 days are randomized to either 12 weeks of PRT followed by 12 weeks of no intervention, or 12 weeks of no intervention followed by 12 weeks of PRT. The primary outcome is change in self-reported pain. Secondary outcomes include hip function, health-related quality of life, use of analgesics, healthcare utilisation, and productivity loss. The analyses will follow the intention-to-treat principle and a mixed-effect model will be applied. CONCLUSION:This is the first randomized trial comparing PRT to no intervention, as well as investigating the effect of delaying PRT, for people with external snapping hip. The trial will evaluate whether PRT reduces pain for people with snapping hip. TRIAL REGISTRATION:ClinicalTrials.gov ID: NCT06924164.
Background: We undertook a randomized controlled trial (RCT) that examined the effects of a remotely-delivered, culturally-tailored exercise training (ET) program on immediate and sustained improvements in patient-reported outcome measures (PROMs) of walking dysfunction, symptoms, and health-related quality of life (HRQOL) among African-Americans with multiple sclerosis (MS).Methods: The study involved a Phase-II, parallel-group, RCT design, and enrolled 123 participants who were randomly assigned into remotely-delivered, culturally-tailored ET (Intervention; n = 63) or stretching and flexibility (Control; n = 60) conditions. The conditions were administered over 4-months by a behavioral coach uninvolved in screening, recruitment, random assignment, or outcome collection. We collected PROMs every 4 months over an 8-month period (baseline, immediate follow-up, 4-month follow-up). The primary PROM was walking dysfunction measured by the 12-item Multiple Sclerosis Walking Scale (MSWS-12).Results: The linear mixed model did not identify a statistically significant interaction between condition and time on MSWS-12 (p = .40). There was a statistically significant time effect on MSWS-12 (p < .005). This coincided with immediate and sustained reductions in MSWS-12 scores compared with baseline for both the Intervention and Control conditions that exceeded the established MCID of 8 points.Conclusion: Our results provide preliminary evidence for the efficacy of two ET approaches for improving walking dysfunction in African-Americans with MS.
Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform a confirmatory analysis within a single trial. Despite their operational advantages, such designs pose serious statistical challenges including control of the family-wise type I error rate and adjusting for selection-induced bias in treatment-effect estimation. We propose a nonparametric bootstrap method for estimating the phase III treatment effect that leverages data from both phases while avoiding reliance on potentially unrealistic parametric assumptions. The proposed estimator is simple and general, and explicitly adjusts for the bias induced by data-driven treatment selection in phase II. Its wide applicability is illustrated through examples involving different types of outcomes. The operating characteristics of the estimator are further evaluated through simulation studies, demonstrating substantially reduced bias compared with the naïve estimator that simply pools data from phases II and III.
BACKGROUND:Migraines rank among the most prevalent neurological disorders worldwide, causing severe functional impairment, predominantly affecting young adults, especially women. Despite pharmacological progress, many individuals continue to experience recurrent attacks, comorbidities, and medication complications, highlighting the need for integrative approaches. Yoga has shown potential benefits in migraine management; however, evidence from rigorous trials using validated migraine-specific modules remains limited. AIM:The trial investigates the effectiveness of a new yoga module as a complementary treatment for migraine symptoms alongside standard medication. METHODS:This single-blind, two-arm randomised controlled trial will recruit 82 participants with migraine per ICHD-3 criteria. Participants will be randomly allocated (1:1) to either a yoga intervention group or a waitlist control group using permuted-block randomisation with sealed-envelope allocation concealment. Outcome assessors will remain blinded. The intervention group will receive a scientifically developed and validated migraine-specific yoga module for 45 min/day, 5 days/week, for 12 weeks, while the control group will continue usual care. Primary outcomes include headache frequency, pill count, pain intensity, migraine-specific quality of life (MSQ v2.1), and calcitonin gene-related peptide (CGRP). Secondary outcomes include endothelial nitric oxide synthase (eNOS), high-sensitivity C-reactive protein (hs-CRP), red cell distribution width (RDW), migraine interictal burden (MIBS-4), and sleep quality (SATED). Assessments will be conducted at baseline and post-intervention. CONCLUSION:This trial will evaluate the effectiveness of a validated migraine-specific yoga intervention on clinical, biochemical, and quality-of-life outcomes. The findings may provide evidence supporting yoga as an integrative adjunctive therapy for migraine management. TRIAL REGISTRATION:CTRI/2025/08/092156 (ctri.gov.in).
INTRODUCTION:Promotion of safe and accessible drinking water in schools shows promise for increasing water intake, reducing sugar-sweetened beverage (SSB) intake, and preventing overweight and obesity. No large-scale studies have evaluated how a water promotion and SSB reduction intervention in childcare centers affects children's weight status. The Healthy Drinks, Healthy Futures study will assess this strategy. METHODS:Following the Social-Ecological Model and Social Cognitive Theory, the Healthy Drinks, Healthy Futures intervention supports changes in childcare and home environments that promote water access while reducing SSB availability. These environmental changes are combined with education for childcare providers and children and brief motivational counseling with parents to reduce SSB consumption and encourage water consumption. Fourteen childcare centers in Santa Clara County, California serving low-income, predominately Latino children ages 2-5 years will participate in this cluster randomized controlled trial. The primary outcome is child BMI Z-score captured at baseline, ~ 6-months and ~ 10 months using anthropometric measures. Dietary outcomes, measured at baseline and ~ 10 months, include intake of water and beverage calories while in childcare (plate waste) and in environments outside of childcare (Automated Self-Administered 24-h dietary recalls). Questionnaires at baseline, ~ 6- and ~ 10-months examine effects on frequency of intake of different beverages. DISCUSSION:This manuscript details the rationale, intervention design, and implementation of the Healthy Drinks, Healthy Futures study. If successful, study results will contribute valuable insights into strategies to promote healthy beverage intake and prevent obesity among young children in childcare centers. CLINICALTRIALS:gov registration number: NCT05112185.
BACKGROUND/AIMS:EGWG is a prevalent and modifiable risk factor for maternal morbidity and mortality. Food insecurity and limited access to healthy foods are key social determinants contributing to EGWG. METHODS:Delivering HOPE is a pragmatic, multi-site randomized controlled trial designed to evaluate whether a food is medicine intervention providing healthy food resources during pregnancy reduces EGWG and associated complications compared with an ESoC. The trial will be conducted in 7 FQHCs. Eligible participants will be pregnant women aged 16-44 years. Participants (N = 1440) will be enrolled and randomized 1:1. Both study arms will receive standardized GWG and nutrition counseling, as well as referrals to food resources. In addition, participants in the Delivering HOPE intervention will receive a directed-spend grocery card that may only be used for purchasing healthy food items aligned with nutritional counseling. The primary outcome is EGWG. Secondary outcomes include dietary intake and pregnancy and delivery complications. A hybrid type 1 effectiveness-implementation will also be conducted and will include qualitative evaluation of implementation barriers and facilitators. This study is grounded in a stakeholder engaged approach and co-led by one academic and one community principal investigator, and an SAAB including women with lived experience, health care providers, payers, state agencies, community-based food organizations, and researchers. CONCLUSIONS:Delivering HOPE addresses a critical gap in evidence by rigorously evaluating a scalable food is medicine intervention during pregnancy in high-risk populations. Findings will inform clinical, payer, and policy decisions regarding food provision as a strategy to improve maternal health equity.
Background Randomised trials that compare a surgical intervention to medical or conservative management occupy a peculiar space in clinical research. The two arms are not symmetric in time: surgery imposes a concentrated, acute risk in exchange for a long-term benefit, whereas conservative management distributes a smaller hazard across the patient's remaining life. In neurosurgery, where the conditions under study are frequently rare and natural histories are measured in decades, this asymmetry exposes weaknesses in conventional trial methodology that have repeatedly led to inconclusive, non-generalisable, or actively misleading results. Discussion Using as illustrations the ARUBA trial of interventional therapy for unruptured brain arteriovenous malformations and the COSS and CMOSS trials of extracranial-intracranial bypass for symptomatic carotid occlusion, we identify the recurrent problems of surgery-versus-conservative trials: contestable equipoise, ambiguous eligibility, heterogeneous interventional arms, mismatched follow-up to the natural history of disease, restricted external validity, and uncritical extrapolation beyond the population actually randomised. We argue that the most consequential of these problems are not statistical but conceptual: investigators repeatedly fail to design trials in which the temporal structure matches the clinical decision the patient is actually making. Conclusion We propose a portfolio of design strategies, several borrowed from oncology, critical care, and cardiology, including expertise-based randomisation, cohort-embedded designs, adaptive designs with informative natural-history priors, platform protocols with a shared control arm, risk-stratified enrichment, and pre-specified lifetime microsimulation. Properly combined, these designs may yield evidence that physicians trust and apply, rather than evidence physicians cite while continuing to operate as before.
Introduction Interpretation of the efficacy of an intervention in clinical trials often relies on whether the p-value for the primary endpoint is <0.05, with less emphasis on the pattern of results across efficacy endpoints. When results across endpoints are consistent and strongly supportive (or unsupportive) interpretation is straightforward. When results vary among endpoints, p-values are nominally statistically significant or slightly greater than 0.05, the standardized effect size is low, or there are divergent results across studies, interpretation is more complicated and relies on individual interpretation, which can introduce bias. Statistical approaches are needed to help interpret the strength of the totality of efficacy results (within a study and across studies). Methods We investigated the properties of a non-parametric approach to testing individual endpoints and a method of combining the individual endpoints into a single test of the overall shift that was then compared to parametric approaches using results from a recent Phase 3 analgesic clinical trial (CLEAR-1 Trial that assessed the efficacy of SP-102 for the treatment of lumbosacral radicular pain). Results Results from these applied methods allowed us to (1) confirm that the observed statistical significance of the primary endpoint in the CLEAR-1 Trial was not driven by pre-defined model assumptions, (2) that a strongly statistically significant result was observed across all endpoints, and (3) that the methods do not simply inflate alpha. Conclusion Statistical approaches such as these are needed to help interpret the strength of the totality of efficacy results quantitatively to support more consistent interpretation of results.
Psychological distress, encompassing PTSD, depression, and anxiety-is highly prevalent among Veterans receiving care in Veterans Health Administration (VHA) primary care settings, yet it frequently goes untreated or undertreated. Traditional psychotherapies and psychiatric medications are often misaligned with Veterans' preferences for self-reliance, low-stigma formats, and skill-based approaches. Primary Care Brief Mindfulness Training (PCBMT) was developed as a brief, transdiagnostic, group-based mindfulness intervention co-facilitated by licensed mental health providers and Veteran peer specialists in VHA primary care. Two preliminary randomized controlled trials (RCTs) demonstrated reductions in PTSD and depression severity relative to control conditions. An ongoing study extends this work through a Hybrid Type I effectiveness-implementation trial at three geographically and demographically diverse VHA sites (Phoenix, San Diego, St. Louis). Three hundred primary care patients with clinically significant psychological distress are being randomized 1:1 to PCBMT or Moving Forward (MF), a transdiagnostic problem-solving group that serves as an active comparison condition. The primary outcome is change in total psychological distress as measured by the Depression Anxiety and Stress Scale (DASS-21) from baseline to post-intervention (8 weeks). Secondary aims will test transdiagnostic mediators (mindfulness, emotion regulation, psychological flexibility, thought suppression) and explore social determinants of health (SDOH) as potential moderators of initiation, completion, and clinical benefit. A qualitative implementation aim, guided by the Consolidated Framework for Implementation Research (CFIR), will characterize barriers and facilitators to support future scale-up. This protocol describes participant selection criteria, intervention conditions, facilitator training, outcome measurement, and analytic strategy. Trial Registration:ClinicalTrials.gov Identifier: NCT-06162741.
BACKGROUND:Shoulder complaints are one of the most common musculoskeletal ailments. Patient-specific characteristics such as obesity, depression and physical labor are established risk factors, whereas imaging findings are common and associations between specific imaging findings and symptomatology is limited. General exercises are considered useful in treatment whereas evidence for specific tendon exercises is lacking. Biopsychosocial model is also recommended, but has not been extensively studied concerning shoulder symptoms. This article describes the study protocol designed to evaluate the effectiveness and the cost-effectiveness of routine and specific physical therapy (PT) interventions. Imaging is performed for descriptive, longitudinal and imaging-symptom correlation studies. METHODS:The Rehabilitation of Shoulder Pain: Evaluation and Clinical Trial (RESPECT) is a randomized three-arm parallel-group study involving 300 participants aged 20 to 60 years with prolonged unilateral shoulder pain. Participants will receive either routine PT, physiotherapist-guided tendon-specific exercise program or psychologically informed PT. Bilateral shoulder radiographs, ultrasound and magnetic resonance imaging will be done at the baseline and at 12 and 36 months. Electronic surveys will be completed at the baseline and at 3, 6, 12 and 36 months. The primary outcome will be patient-specific functional scale (PSFS) at 12 months, analyzed using analysis of covariance (ANCOVA), adjusted for baseline PSFS. DISCUSSION:RESPECT will provide systematic and controlled data regarding different PT interventions in prolonged shoulder symptoms, which is currently limited. Being one of the most common sources of musculoskeletal pain, improved management could reduce symptom-related burden and prolonged functional impairment at individual and population level. CLINICALTRIALS:gov; Registration number NCT07235969; Registered November 18th, 2025; Version: 1.0.
Background Hypersensitivity Pneumonitis (HP) is an interstitial lung disease caused by an inhalational environmental exposure. Patients living with HP experience significant stress, uncertainty, and hypervigilance about the management of their disease and prognosis. These factors lead to reduced health-related quality of life (HRQOL), an important outcome that no interventions currently target. Objective The goal of this behavioral and educational intervention, RISE-HP, is to improve HRQOL in people who have HP. The objective of this pilot study is to assess feasibility, acceptability, and preliminary effectiveness of the RISE-HP intervention. Methods This pilot randomized controlled trial will be conducted in patients over the age of 18 with a diagnosis of HP. Forty participants will be randomly assigned to receive either the RISE-HP intervention (meetings with a peer coach focused on living well with their HP using cognitive behavioral techniques and motivational interviewing) or an attention control (general health education sessions with a research assistant) for 10 weeks. Participants will complete four additional study visits (enrollment, 5 weeks, 10 weeks, and 14 weeks after intervention start) for patient reported outcome measure completion. Primary implementation outcomes will be feasibility and acceptability. Secondary patient-centered effectiveness clinical outcomes will be improvement in HRQOL as measured by the Kings Brief Interstitial Lung Disease (KBILD) questionnaire. Additional secondary patient-reported clinical outcomes include fatigue, anxiety, depression, and self-efficacy. Conclusion Overall, this study addresses an important gap in HP care by targeting HRQOL and offers a novel non-pharmacologic patient-centered approach to therapy in patients with HP.
Diabetes and hypertension frequently coexist, greatly increasing cardiovascular and mortality risk. The optimal dietary strategies for blood pressure (BP) control in people with diabetes remain uncertain. This report details the rationale and design of the Dietary Approaches to Stop Hypertension for Diabetes (DASH4D) trial, a randomized, controlled, crossover feeding study designed to evaluate the effects of the DASH4D dietary pattern and sodium content on BP among adults with type 2 diabetes. The DASH4D dietary pattern was developed by adapting the DASH diet, an effective diet for BP lowering, to maximize efficacy and safety in a diabetes population. The DASH4D trial randomized participants to a sequence of four 5-week feeding periods testing the following diets: 1) DASH4D diet with lower sodium, 2) DASH4D diet with higher sodium, 3) comparison (typical US) diet with lower sodium, and 4) comparison diet with higher sodium (primary contrast: 1 vs. 4). Diets were tailored to meet specific nutrient targets, and calories were adjusted to maintain stable weight. The primary outcome was systolic BP, and the secondary outcome was diastolic BP. Key additional outcomes included measures of glycemia, lipids, proteinuria, and diet acceptability. The study design addressed multiple challenges including conducting controlled feeding in a medically complex population, maximizing dietary adherence, and implementation during the COVID-19 pandemic. This design provides a road map to rigorously evaluate the efficacy of nutritional interventions in people with diabetes, and generates critical evidence to inform guidelines and clinical practice around the optimal dietary strategies to control diabetes and hypertension.
To examine American Indian/Alaska Native (AI/AN) adults' attitudes and beliefs on research and clinical trial participation, we administered surveys at four AI/AN cultural events in Seattle, WA and Denver, CO, between 2022 and 2024. Surveys assessed familiarity with, attitudes towards, and beliefs about clinical trials, as well as health behaviors, research participation, and demographic characteristics. A total of 1287 AI/AN adults completed surveys. We performed logistic regression to examine the association between each attitude or belief and willingness to participate in clinical trials. Overall, 75% of participants reported familiarity with clinical trials and 61% reported at least some willingness to participate in a clinical trial. Most participants (74%) agreed that clinical trials are important to improving health and healthcare; however, two-thirds said they would participate only if they thought that their community and future generations would benefit from the research. Participants who believed representation in clinical trials was important to ensure that treatments work for people like them had greater odds of reporting willingness to participate (OR: 6.81; 95% CI: 5.25-8.84). Attitudes and beliefs varied according to gender and urbanicity. Some attitudes and beliefs are more prevalent among individuals willing to participate in clinical trials. Findings may not generalize beyond powwow attendees, and reported willingness may not translate into actual clinical trial enrollment. Engaging communities to determine acceptable procedures may improve recruitment efforts. Moreover, researchers should work with communities to ensure that community members and future generations benefit from research to help increase AI/AN representation in clinical trials.
Buprenorphine treatment for opioid use disorder (OUD) is highly effective in decreasing opioid use, risk of opioid overdose, and death, but retention is challenging. Buprenorphine does not always eliminate illicit opioid use and craving and does not treat stimulant or other substance co-use, nor common comorbid sleep problems. Tirzepatide, a glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, may help address substance use and sleep problems. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting a 9-site outpatient, intent-to-treat, two-arm, double-blind, randomized controlled trial: Evaluation of Tirzepatide as an Adjunct to Buprenorphine for the treatment of OUD (TAB). The primary objective is to evaluate the effect of tirzepatide, relative to placebo, as an adjunct to buprenorphine on retention and on substance-related and sleep outcomes in adults with OUD. The primary outcome is 6-month buprenorphine treatment retention. The key secondary outcome is proportion of illicit opioid-negative urine samples over the 6-month treatment period. Approximately 310 adults with moderate-severe OUD who recently started buprenorphine will be recruited and randomized 1:1 to tirzepatide or placebo, balancing on site and buprenorphine formulation (transmucosal vs extended-release). Participants will be administered study medication, receive Fitbits to track sleep, and attend weekly research visits through 6 months post-randomization with longer research visits occurring at 1, 3, and 6 months. A follow-up visit at week 30 will collect final safety measures. This paper describes the rationale and study design for TAB, the first randomized trial to test tirzepatide for the treatment of OUD.
BACKGROUND:Posttraumatic stress disorder (PTSD) is a significant risk factor for suicide among veterans, but there is a critical knowledge gap about how to treat PTSD in the context of elevated acute suicide risk. Prior research suggests that a treatment that combines Dialectical Behavior Therapy (DBT) with the DBT Prolonged Exposure protocol (DBT PE) reduces PTSD and self-directed violence (SDV) among high-risk individuals while also being feasible, acceptable, and safe to deliver. However, a large-scale randomized controlled trial is needed. This study will compare the effectiveness of DBT + DBT PE to the current gold standard of care in the Veterans Health Administration (VHA), Prolonged Exposure therapy augmented with suicide risk management (PE + SRM), while also examining barriers and facilitators to implementing these treatments in VHA. METHODS:This multi-site hybrid type 1 effectiveness-implementation trial will randomize 125 veterans with PTSD, recent and repeated SDV, suicidal ideation, and emotion dysregulation to DBT + DBT PE (12 months) or PE + SRM (up to 20 weeks). Participants will be treated at 4 VHA sites and evaluated by masked assessors at 5 points over 16 months. Implementation determinants will be assessed among veterans, providers, and administrators using a mixed methods approach. RESULTS:The project is ongoing and results will be reported in future manuscripts. CONCLUSION:This project will yield generalizable knowledge about how to safely and effectively treat PTSD among individuals at elevated acute risk of suicide as well as how to maximize future implementation success if either treatment is found effective. TRIAL REGISTRATION:ClinicalTrials.govNCT05974631, date of registration July 25, 2023, https://clinicaltrials.gov/study/NCT05974631.
Latinx adolescents with type 1 diabetes (T1D) have lower diabetes technology use and less optimal health outcomes compared to non-marginalized populations. In keeping with the tenants of social cognitive theory, adolescents with T1D who participate in virtual peer groups (VPGs) experience improved outcomes and technology use, but VPGs have not been developed or tested specifically in a Latinx cohort. Our previous focus groups with Latinx adolescents and caregivers revealed an urgent need for community-building, support, and culturally relevant information on multiple T1D topics, including diabetes technology. Through a community-engaged research process we developed a VPG intervention - Device use Reimagined through Education And Mentorship (DREAM) - for Latinx adolescents with T1D and their caregivers, and designed a pragmatic trial to assess the impact of this intervention. VPG content was created for both age groups and in two languages through an iterative approach with input from a multi-site community advisory council. VPG sessions covered six topics within T1D self-care, and were delivered to participants over 6-12 months. VPG facilitator recruitment prioritized linguistic and cultural congruence with participants as well as personal or professional experience with T1D. Clinical trial design was heavily influenced by stakeholder input which prioritized opportunities for community-building outside of the clinical environment. The resulting clinical trial will yield important information about how to engage a historically underrepresented group in clinical research, and build essential knowledge about the utility of VPG interventions to narrow existing disparities in T1D care.
BACKGROUND:Despite widespread insurance coverage and USPSTF recommendations, less than 20% of eligible individuals undergo annual lung cancer screening nationally. This low uptake suggests that innovative screening modalities and referral pathways are needed. We hypothesize that utilizing community pharmacies for screening and connecting patients to either traditional imaging or novel, blood-based modalities will improve uptake among eligible patients. METHODS:We describe a multiphase study. First, during the initial phase, to assess the feasibility of community pharmacist-led lung cancer screening (LCS) and, subsequently, a randomized stepped-wedge trial expansion phase comparing pharmacist LCS intervention to usual care in ten community pharmacies. We plan to enroll 250 participants in the initial phase and 1000 participants in the expansion phase (approximately 500 participants in the usual care arm and 500 participants in the intervention arm). The primary endpoint is the proportion of LCS-eligible participants who receive a screening recommendation from a pharmacist and who both accept the recommendation and complete the screening. DISCUSSION:This study will test the feasibility and efficacy of pharmacy-based LCS programs. By investigating an alternative LCS referral location and modality, our novel intervention seeks to supplement traditional primary care-based interventions to increase overall LCS rates. We hypothesize that this strategy can increase LCS rates from 20% to 40% of eligible participants.
BACKGROUND:Transthoracic echocardiography (TTE) is the most commonly performed cardiac imaging modality with over 30 million studies annually. Demand for timely expert interpretation continues to outpace capacity, creating diagnostic delays and inter-observer variability that impact patient care. Recent research has suggested computer vision artificial intelligence (AI) models can generate accurate preliminary comprehensive TTE reports, however, prospective evaluation is needed to determine whether AI-assisted TTE interpretation can improve clinician efficiency while preserving diagnostic accuracy. METHODS:AI ECHO INSIGHT is a prospective randomized blinded clinical trial conducted at Kaiser Permanente Northern California that will evaluate 1200 historical TTE studies (1000 consecutive unselected studies plus 200 with moderate or greater valvular disease) interpreted using three workflows: (1) AI-generated preliminary report finalized by a blinded cardiologist (AI-assisted); (2) cardiologist-generated preliminary report finalized by a blinded cardiologist (cardiologist-assisted); and (3) sonographer-generated preliminary report finalized by a blinded cardiologist (sonographer-assisted). The primary outcome is the rate of substantial change between preliminary and final reports, comparing the AI-assisted workflow to the pooled cardiologist-assisted and sonographer-assisted workflows. Secondary outcomes include cardiologist interpretation time for report finalization, superiority testing for diagnostic accuracy, and reporting consistency. CONCLUSION:AI ECHO INSIGHT is a prospective randomized blinded clinical trial evaluating the clinical impact of AI-assisted TTE interpretation on diagnostic accuracy, cardiologist efficiency, and reporting consistency in real-world echocardiography workflows. TRIAL REGISTRATION:ClinicalTrials.gov registration number NCT07229300.
