Late-breaking Clinical Trials Research Articles

Functional improvement of non-infarct related coronary artery stenosis by extensive LDL-C reduction with a PCSK9 antibody: the FITTER trial, microvascular function analysis

Abstract Background Atherosclerosis and microvascular dysfunction are closely linked. Moreover, impaired microvascular function is strongly associated with increased risk on major adverse cardiac events. In patients presenting with acute coronary syndrome (ACS), microvascular function is reduced. PCSK9-inhibitors have shown to reduce plaque burden and lipid load in epicardial vessels and might exhibit similar results on microvascular vessels, thereby improving microvascular function. The FITTER trial offers the unique opportunity to test this hypothesis. Methods The FITTER trial is a multi-center, randomized, double blind, placebo controlled clinical trial for patients presenting with ACS and multi-vessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) measurement of non-infarct related artery (non-IRA) lesions was performed. Patients with intermediate, non-critical lesions (FFR: 0.67-0.85) were included in this trial. For exploratory purpose, additional physiological assessment of the non-IRA included coronary flow reserve (CFR) and microvascular resistance index (IMR) measurements. Microvascular function was evaluated using a pressure- and temperature-sensitive guidewire and a bolus thermodilution method. Participants were randomized and treated for 12 weeks with either evolocumab or placebo in addition to high-intensity statin therapy. Staged reevaluation was done at 12 weeks. After repeated physiology testing, PCI was performed if deemed necessary. Pre-defined exploratory analysis includes the absolute and relative difference in change between CFR and IMR from baseline to follow up in the non-IRA. PCSK9 inhibition might result in a relatively larger increase of CFR and larger decrease of IMR. Results Between March 2020 and August 2023, a total of 150 patients were included in the trial. In 61 patients (88.5% male, age 65.3 ± 9.1 years, 23.0% STEMI, 70.5% non-STEMI, 6.6% UAP) successful baseline and follow-up measurements of microvascular function were performed. Complete results will be available at the beginning of March 2024. The primary- and secondary endpoints will be submitted for late-breaking clinical trials selection. The results of this abstract will include a per vessel analysis of coronary artery microvascular function. Conclusion The FITTER trial will provide new insights on the potential of extensive LDL-C reduction with a PCSK9 antibody on microvascular coronary artery function in patients presenting with ACS and MVD.

Late-Breaking Clinical Trials LB-469809: Late-Breaking Clinical Trials and Science - Ablation

Late-Breaking Clinical Trials LB-469809: Late-Breaking Clinical Trials and Science - Ablation

Late-Breaking Clinical Trials LB-469807: Late-Breaking Clinical Trials and Science - CIEDs

Late-Breaking Clinical Trials LB-469807: Late-Breaking Clinical Trials and Science - CIEDs

Late-Breaking Clinical Trials LB-469805: Late-Breaking Clinical Trials and Science - Innovation

Late-Breaking Clinical Trials LB-469805: Late-Breaking Clinical Trials and Science - Innovation

Late-Breaking Clinical Trials LB-469804: Late-Breaking Clinical Trials and Science - Ablation

Late-Breaking Clinical Trials LB-469804: Late-Breaking Clinical Trials and Science - Ablation

CLDN6 CAR-T cell therapy of relapsed/refractory solid tumors ± a CLDN6-encoding mRNA vaccine: Dose escalation data from the BNT211-01 phase 1 trial using an automated product.

2518 Background: We are developing a chimeric antigen receptor (CAR)-T cell therapy targeting claudin 6 (CLDN6), an oncofetal antigen that is undetectable in healthy somatic tissue and highly expressed in various solid cancers. Autologous CLDN6 CAR-T cells are being tested alone and in combination with CLDN6-encoding CAR-T cell Amplifying RNA Vaccine (CARVac), a nanoparticulate RNA vaccine designed to stimulate and expand CLDN6 CAR-T cells. Methods: The ongoing first-in-human trial BNT211-01 evaluates the safety and feasibility of CLDN6 CAR-T cell transfer ± CARVac in lymphodepleted patients with relapsed/refractory solid tumors. Patients are pre-screened for CLDN6 expression with a cut-off of 50% positivity of intermediate or strong intensity by immunohistochemistry staining. Key endpoints are safety, tolerability, and anti-tumor activity. Pharmacokinetics of adoptively transferred CAR-T cells in peripheral blood is monitored by quantitative PCR. Dose escalation proceeds according to a classical 3+3 design, testing CLDN6 CAR-T cells at each dose level as both as monotherapy and in combination with CARVac. We previously reported results from 22 patients from 4 dose escalation cohorts with a manual CAR-T production process ± CARVac (ESMO-IO LBA38) which followed the same methodology. We observed durable responses along with a manageable safety profile, in line with commercial CAR-T products used to treat B-cell malignancies. No on-target/off-tumor toxicity and only a single case of (grade 1) neurotoxicity was observed. Given the encouraging efficacy, we have implemented an automated process to scale-up manufacturing. Accordingly, we are repeating the dose escalation with an automated CAR-T cell product, and with a modified CARVac regimen. As of 1st February 2023, 7 patients with epithelial ovarian carcinoma (EOC), 4 with testicular germ cell tumors (GCT), and a further 5 patients with tumors of various indications have been infused with CAR-T cells up to DL2. We intend to submit efficacy, safety and CAR T-cell pharmacokinetics data from 5 cohorts treated with 1x106, 1x107 or 1x108 CLDN6 CAR-T cells ± CARVac with a data cut-off of March 14th, 2023 from ≥17 treated patients as a late-breaking abstract. Clinical trial information: NCT04503278 .

Late-Breaking Clinical Trials LB-456088: Late-Breaking Clinical Trials and Science - Registry - CIED

Late-Breaking Clinical Trials LB-456088: Late-Breaking Clinical Trials and Science - Registry - CIED

Late-Breaking Clinical Trials LB-456640: Late-Breaking Clinical Trials and Science - Innovations

Late-Breaking Clinical Trials LB-456640: Late-Breaking Clinical Trials and Science - Innovations

Late-Breaking Clinical Trials LB-456089: Late-Breaking Clinical Trials and Science - Ablation

Late-Breaking Clinical Trials LB-456089: Late-Breaking Clinical Trials and Science - Ablation

Underrepresentation of Women in Late-Breaking Cardiovascular Clinical Trials.

Background: Cardiovascular disease is the leading cause of mortality for women and men. Prior studies have demonstrated the underrepresentation of women in published clinical trials, but no study to date has assessed inclusion of women in late-breaking clinical trials (LBCTs) presented at national meetings. The objective is to characterize the inclusion of women participants in LBCT presented at the 2021 American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC) annual meetings and identify trial characteristics associated with improved inclusion. Methods: LBCT presented at the 2021 ACC, AHA, and ESC meetings were identified and the inclusion of women as participants was assessed. The inclusion to prevalence ratio (IPR) was calculated by dividing the percentage of women participants by the percentage of women in the disease population. IPRs <1 indicate underenrollment of women. Of the 68 LBCT, 3 trials were excluded due to lack of subject matter relevance. Results: Inclusion of women ranged from 0% to 71%. Only 47.1% of trials reported sex-specific analyses. The average IPR was 0.76 for all trials and did not vary based on conference, trial center, geographic region, or funding source. The average IPR varied based on subspecialty, with a statistical difference between interventional cardiology and heart failure (0.65 vs. 0.88, p = 0.02). The average IPR was significantly lower for procedural studies compared with medication trials (0.61 vs. 0.78, p = 0.008), as well as for studies with mean age <65 and trial size <1500 participants. There was no difference in IPR based on female authorship. Conclusions: LBCT can impact novel drug and device approval, intervention indications, and patient management. Nonetheless, most LBCT underenroll women, particularly, procedural LBCT. In 2021, sex-based enrollment disparities persist, highlighting the need to engage key stakeholders, including funding organizations, national governing bodies, editorial board members, and medical societies, in the creation of a coordinated strategic initiative to advance gender parity. These findings warrant further investigation to increase inclusion of women in trials, including potential enrollment requirements for consideration as LBCT by meeting organizers.

Most Recent Trials and Advances in Hypertension.

Hypertension is one of the most prevalent cardiovascular risk factors and blood pressure control remains a clinical challenge, especially for patients with established cardiovascular disease. Late-breaking clinical trials and other evidence in hypertension have evolved to assess the most accurate ways to measure blood pressure, the use of combination therapies, considerations in special populations and evaluation of new techniques. Recent evidence supports the superiority of ambulatory or 24-hour blood pressure measurements, rather than office blood pressure measurements, for the assessment of cardiovascular risk. The use of fixed-dose combinations and polypills has been demonstrated to be valid and to provide clinical benefits beyond blood pressure control. There have also been advances in new approaches such as telemedicine, devices and the use of algorithms. Clinical trials have provided valuable data on blood pressure control in primary prevention, during pregnancy and in the elderly. The role of renal denervation remains unsolved but innovative techniques using ultrasound or alcohol injections are being explored. Current evidence and results of latest trials are summarised in this review.

Women in cardiology leadership of randomized clinical trials and participation of women in late-breaking clinical trials: has the COVID-19 pandemic changed a thing or not exactly?

Abstract Introduction Despite considerable developments made in the representation of women in cardiology (WIC) recently, there still remain substantial disparities in the representation of women participants in clinical trials, as well as women physicians and scientists in clinical trial leadership. Under-representation of women in Randomized Clinical Trials (RCTs) remains the bane of the modern medicine, impeding the development of sex-specific guidelines in cardiovascular diseases. Female leadership in clinical trials has been shown to enhance the inclusion of women as trial participants. Furthermore, while the COVID-19 pandemic has impacted women in academia, there is no data thus far reporting the impact of the pandemic in terms of presenters and leadership of late-breaking clinical trials (LBCT) in cardiology during this period. Purpose We aimed to determine inclusion of WIC in LBCTs leadership and their correlation to inclusion of women in reported RCTs. Methods In our comprehensive analysis, we included all LBCTs presented at major international cardiovascular meetings reported over the period of January 2020 to February 2022. Data were derived from the original presentation at the meeting and/or simultaneous/ subsequent publication of manuscript. Sex of the presenter (woman or man), was assessed by either original videos of the presentation at the meeting, or based on pronoun use in the biographies derived from institutional profiles. The presence or absence of reporting of sex distribution of study participants were also recorded from original presentation at the meeting and/or published manuscript. Proportion of women included in each trial was sourced from either original publication or calculated from any similar data shown during the presentations. Results A total of 400 of RCTs from 19 meetings were included with a total of 400 presenters/principal investigators recorded – 32 (8%) women and 368 (92%) men. There were no significant differences between 2020 and 2021 [15 (7.2%) women in 2021 vs. 17 (19.3%) in 2020 (P=0.446)]. Proportions of women included in RCTs with WIC (37.3%) vs. non-WIC (38.7%) presenters were comparable (p=0.559), while 45% of RCTs didn't report sex distribution of participants. Except for 2 meetings (CRT 2020 and 2022), all others were virtual. Conclusion WIC representation as RCTs presenters was significantly low, despite the opportunity of virtual attendance afforded during the COVID-19 pandemic. Modest inclusion of women irrespective of sex of RCT leadership emphasizes multi-level problems that require more actionable solutions: i.e. implicit bias training started as early as medical school, continuing education on necessity for diversity, equity and inclusion, patient and public involvement, and comprehensive guidance on trial design, such that future RCT participants reflect the populations intended to treat. Funding Acknowledgement Type of funding sources: None.

Late breaking clinical trials at ACC 22.

Late breaking clinical trials at ACC 22.

POS-546 EFFICACY AND SAFETY OF IPTACOPAN IN IgA NEPHROPATHY: RESULTS OF A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 2 STUDY AT 6 MONTHS

No approved targeted therapies currently exist for IgA nephropathy (IgAN). Targeting the alternative complement pathway (AP) is an attractive therapeutic strategy given its role in the pathogenesis of IgAN. Iptacopan (LNP023) is a first-in-class, oral, potent and highly selective inhibitor of factor B of AP. This randomized, double-blind, dose-ranging, parallel-group adaptive design Phase 2 study (NCT03373461) enrolled patients with biopsy-confirmed IgAN (within the previous 3 years), urine protein-to-creatinine ratio (UPCR) ≥0.8 g/g or urine protein ≥0.75 g/24 h, and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. Part 1 of the study enrolled patients for a 3-month treatment period; Part 2 of the study enrolled patients for a 6-month treatment period; both Parts comprised a 3-month treatment-free follow-up. Patients were randomized to one of the four iptacopan arms (10, 50, 100 [in Part 2 only], and 200 mg bid) or placebo. In this analysis, we report efficacy and biomarker data assessed at 6 months and treatment-emergent adverse events (AEs) assessed for the entire study duration. In addition to the pre-specified efficacy analysis of Part 2 at 6 months, Post hoc analyses combining data from Parts 1 and 2 were also performed. 46 and 66 patients were randomized in Parts 1 and 2, respectively. In Part 2, 58 patients completed 6 months of treatment. Demographic and baseline characteristics were generally well-balanced across all arms. The primary analysis yielded a statistically significant dose-response effect (1-sided p=0.038) of iptacopan versus placebo at 3 months, with maximal reduction in UPCR achieved with iptacopan 200 mg bid (23%; 80% CI: 8–34% using MCP-mod; Primary results were presented at 58thERA-EDTA Congress 2021 as late-breaking clinical trial ). UPCR continued to decrease between 3 and 6 months in the higher dosed iptacopan arms in Part 2, albeit with a wider 80% CI reflecting the smaller sample size. To allow better comparison with the primary analysis at 3 months, a Post hoc analysis of pooled data from Parts 1 and 2 was performed. The results indicated UPCR reduction from baseline up to 6 months in iptacopan 200 mg bid arm by up to 40% (80% CI: 16–53% using MCP-mod model) and at least 28% (80% CI: 3–46% using MMRM model) versus placebo (Figure 1). Sustained inhibition of AP biomarkers including plasma Bb, serum Wieslab, and urinary C5b-9 through 6 months was also observed with all doses of iptacopan above 10 mg bid (Figure 2). Iptacopan had a well-tolerated safety profile, with no deaths, no serious adverse events (SAEs) suspected to be treatment-related, and no serious infections caused by encapsulated bacteria. Iptacopan was well tolerated and led to continuous reduction in proteinuria and strong inhibition of AP activity through 6 months in patients with IgAN. These data are consistent with previous findings from the interim analysis at 3 months and support further evaluation of iptacopan in the ongoing Phase 3 APPLAUSE-IgAN trial (NCT04578834).

Abstract 11028: Gender Inequality in Enrollment in Late-Breaking Cardiovascular Clinical Trials

Introduction: Cardiovascular disease is the leading cause of mortality in both men and women. Prior studies have demonstrated the underrepresentation of women in published clinical trials, but to date no study has assessed inclusion of women in late-breaking clinical trials (LBCT) presented at national meetings. Methods: Using the American College of Cardiology’s 2021 Scientific Sessions’ LBCT, the inclusion of women was assessed. The inclusion to prevalence ratio (IPR) was calculated by dividing the percentage women participants in the trial by the percentage women in each disease population. IPRs less than 1 indicate under-enrollment of women. Of the 26 LBCT, 1 trial was excluded, as it exclusively enrolled women. Results: Inclusion of women ranged from 16.8% to 53.1%. The average IPR was 0.71 for all trials and did not vary based on single vs. multi-center, size, or funding source. The average IPR varied based on sub-specialty, with statistical differences noted between electrophysiology (EP) and heart failure (0.53 vs 0.86, p=0.02), as well as between EP and general/preventive (0.53 vs 0.72, p=0.04). The average IPR was significantly lower for procedural studies compared with medication trials (0.51 vs 0.73, p=0.02). There was no difference in IPR based on female authorship (Figure 1). Conclusions: LBCT can impact novel drug/device approval, indications, and patient management. Nonetheless, most LBCT under-enroll women. In particular, EP, interventional cardiology, and procedural LBCT have the lowest inclusion of women. These findings warrant further investigation into ways to increase enrollment of women, including potential requirements for consideration as LBCT by meeting organizers.

Late-Breaking Clinical Trials and Registry

Late-Breaking Clinical Trials and Registry

Late-Breaking Clinical Trials Updates

Late-Breaking Clinical Trials Updates

SAT-485 NEW METHODS OF CONFERENCE COVERAGE ON SOCIAL MEDIA –DO THEY HELP INCREASE THE REACH?

Over the past decade, there is an increase in the utilization of various Social Media (SoMe) platforms in disseminating & sharing information from medical conferences. Twitter’s popularity among nephrologists for this purpose is widespread. At the World Congress of Nephrology (WCN) in Mexico in April 2017, a SoMe Task Force was created by the International Society of Nephrology (ISN). One of the main objectives of this was a comprehensive coverage of the lectures & presentations shared via different SoMe platforms. In a similar manner, an ISN WCN SoMe Team was created to cover the World Congress of Nephrology in Melbourne in April 2019 to disseminate scientific info from the conference. The ISN WCN SoMe Team launched Poster Talks (PTs), where the Author gives a voice over describing the poster. Also, Visual Abstracts (VA) of posters/oral papers & live talks (Live VAs) were created. Interviews of speakers & poster presenters as well as live stream of late breaking clinical trial (LBCT) were additional distinctive methods adopted. This was the first time Facebook was used to extend an international nephrology conference’s reach & its own analytics were used. Twitter analysis of these newer methods were done using Symplur & NOD Analytics. Periscope and YouTube data was analyzed looking at interviews & how they impacted on information spread. Over 17000 tweets from the conference were accessed in 90 countries (see figure 1). There were 1943 unique participants. There were 34 video interviews - 25 poster interviews & 9 speaker interviews. An index for the quantity of education delivered during these interviews was created (see figure 2). 21 Poster Talks and 29 VAs were created, (21 poster VAs & 8 Live VAs). When compared, these new methods of coverage were accessed, retweeted and commented upon more frequently than traditional slide-based tweets. YouTube data analysis showed 696 unique viewers and 824 min watch time. Highest attention span was of 3:21. Facebook data analysis showed that the Social Media reach was 340K, with 1786 interactions, 30 shares & 1720 likes. Live stream data of LBCT showed 2713 playbacks with 587 peak concurrent viewers, 798 hours of total view time with an average session length of 17.6 min with participants from 59 countries tuning in, generating a volume of more than 7000 tweets.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The newer methods of Social Media information dissemination from Conferences namely Poster Talks, Interviews, Visual Abstracts, Late Breaking Clinical Trials - Live streams as well as adding Facebook and & Youtube as platforms of sharing, helped increase the interaction and & reach of the conference to a significant extent.

Major Cardiovascular Advances: Highlights from the 2019 American College of Cardiology Annual Scientific Session

The 69th American College of Cardiology Annual Scientific Session and Expo was held in New Orleans, Louisiana on March 16–18, 2019. For many years this meeting has gathered together an enormous number of participants, abstracts, oral presentations, poster presentations, educational sessions, late-breaking clinical trial results, and clinical practice guidelines under one roof. The authors have selected and summarized the key points from a number of key landmark trials, featured clinical research results and clinical practice guidelines that were presented during this year’s meeting.

Late-breaking clinical trials

Background: The Zilver® PTX® stent with polymer-free paclitaxel coating is the first drug-eluting stent approved (currently CE marked, investigational in the United States and Japan) for the superficial femoral artery (SFA). This multicenter, multinational, prospective, randomized trial compared the safety and effectiveness of the Zilver PTX study to balloon angioplasty (PTA) and bare metal stenting (BMS). Methods: Symptomatic patients with SFA lesions (de novo or non-instent restenosis) were randomized to PTA or Zilver PTX stent placement. PTA patients experiencing acute failure (e.g. 30% residual stenosis) underwent secondary randomization to provisional stenting with Zilver BMS or Zilver PTX. Follow-up included event-free survival (EFS), and primary patency by Duplex ultrasound core laboratory analysis (peak systolic velocity ratio 2.0). Results: 479 patients were enrolled at 55 institutions in the United States, Japan and Germany, with 241 patients randomized to the Zilver PTX group and 238 to the PTA group. Demographics and lesion characteristics (e.g., lesion length 66 mm and 63 mm, respectively) were similar for the groups. Approximately half the PTA group experienced acute failure and underwent secondary randomization; 59 and 61 patients were assigned to provisional stenting with Zilver BMS and Zilver PTX, respectively. The study results met the 12-month primary endpoint goals showing non-inferior EFS (90.4% versus 82.6%, p 0.01) and superior primary patency (83.1% and 32.8%, p 0.01) for the Zilver PTX compared to PTA. The randomized comparison of provisional stenting with Zilver PTX versus Zilver BMS also showed significant paclitaxel coating benefit, with 12-month patency rates of 89.9% and 73.0% respectively (p 0.01). Currently, 24-month follow-up is available for 278 patients, showing an 86.6% EFS rate and a 74.8% patency rate. The randomized comparison of provisional stenting with Zilver PTX versus Zilver BMS continues to demonstrate significant paclitaxel coating benefit at 24 months, with patency rates of 81.2% and 62.7% respectively (p 0.01). Conclusion: The results of this randomized, multicenter study support the safety and effectiveness of the Zilver PTX Drug-Eluting Peripheral Stent.