Hartford

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are evaluating the effectiveness of a long-acting injectable form of buprenorphine compared to the daily sublingual under the tongue buprenorphine in treating Veterans with moderate to severe opioid use disorder OUD. This open-label, randomized controlled trial aims to see which treatment better retains Veterans in opioid therapy and helps sustain opioid abstinence. The study also examines secondary outcomes such as substance use, overdose incidents, infectious disease testing, psychiatric symptoms, housing status, dental health, and cost-effectiveness. Participants are Veterans aged 18 and older diagnosed with moderate to severe OUD and beginning a new treatment episode. After an induction period on daily sublingual buprenorphine, participants are randomly assigned to receive either a 28-day supply of daily sublingual buprenorphine or a monthly injectable buprenorphine shot administered in the clinic. Doses for the injectable form target 300mg, with a 100mg option for those who cannot tolerate the higher dose. Study visits occur weekly during the first month, then every two weeks until week 52, including medication management. Throughout the 52-week active phase, participants report opioid use and provide urine samples every two weeks to evaluate abstinence and treatment retention. Additional assessments include HIV, Hepatitis B and C testing, psychiatric questionnaires, risk behavior evaluations, and dental health surveys. After the active phase, participants are followed passively using medical records for up to 10 years to monitor long-term outcomes. The study expects to recruit 952 Veterans over 7 years across multiple VA Medical Centers.

Researchers are investigating treatments for patients with stage IV or recurring non-small cell lung cancer who have previously received platinum chemotherapy and immunotherapy. This phase IIIII trial compares the effects of adding cemiplimab, an immune system-stimulating monoclonal antibody, to the usual combination of docetaxel and ramucirumab. The goal is to see if adding cemiplimab helps the immune system better attack tumor cells and improves survival outcomes. Participants are randomly assigned to one of two groups. One group receives docetaxel and ramucirumab along with dexamethasone, while the other group receives these same treatments plus cemiplimab. Treatments are given in cycles every 21 days, with infusions lasting from 30 minutes to an hour depending on the drug. Patients undergo regular blood sample collections and imaging scans such as CT or MRI throughout the study. During the trial, participants are monitored for overall survival, disease progression, tumor response, and side effects. After completing treatment, follow-up visits occur every 3 to 6 months for up to 3 years. Blood tests and imaging help assess treatment effects and safety. Researchers also collect and store blood and tissue samples to support future studies.

Researchers are evaluating treatments for older adults aged 70 and above with advanced stage IIIB-IV non-small cell lung cancer that expresses PD-L1 in 1-49% of tumor cells. This phase III trial compares the effects of adding chemotherapy to immunotherapy with pembrolizumab against pembrolizumab alone. The study aims to assess improvements in overall survival, progression-free survival, response rates, toxicity, quality of life, and explore geriatric assessment factors and gut microbiome correlations. Participants are randomly assigned to one of two groups. Arm A receives pembrolizumab intravenously every 21 days for four cycles, followed by maintenance pembrolizumab every 21 or 42 days for up to two years. Arm B receives the same pembrolizumab schedule plus one of several chemotherapy regimens, including combinations of pemetrexed, carboplatin, nab-paclitaxel, or paclitaxel administered intravenously on different schedules for four cycles, followed by pembrolizumab maintenance. Imaging with MRI, CT, and PET scans is performed at baseline and throughout the trial. During the study, participants undergo regular assessments including imaging scans to monitor disease status, blood tests, and quality of life questionnaires. After treatment completion, follow-up visits occur every three months for up to two years and then every six months up to five years. Researchers measure overall survival as the primary outcome and also track progression-free survival, response rates, adverse events, and patient-reported quality of life. Safety and tolerability are closely monitored along with exploratory analyses of chemotherapy dose intensity and microbiome factors.

Researchers are evaluating glecaprevirpibrentasvir GLEPIB, a direct-acting antiviral originally used to treat chronic hepatitis C infection, for its potential to improve symptoms in people with posttraumatic stress disorder PTSD who do not have hepatitis C. This double-blind randomized placebo-controlled trial aims to determine if GLEPIB can reduce PTSD symptoms and improve daily functioning, while also assessing the safety and tolerability of this treatment for PTSD. In this study, 92 participants diagnosed with PTSD will be randomly assigned to receive either GLEPIB or a placebo. Those receiving GLEPIB will take 3 oral tablets daily 100 mg glecaprevir and 40 mg pibrentasvir for 8 weeks. The placebo group will take matching inactive tablets for the same duration. Participants and researchers will not know which treatment is being given to ensure unbiased results. Throughout the 8-week treatment period, participants will be evaluated using the Clinical Administered Post-Traumatic Stress Disorder Scale version 5 CAPS-5 to measure changes in PTSD symptoms, and the World Health Organization Disability Assessment Schedule WHODAS to assess functioning. Safety and tolerability will be monitored closely. The total study participation involves regular assessments during and after the treatment period to track symptom changes and any side effects.

Researchers are evaluating the CxBladder Monitor and Monitor urinary biomarker tests to detect recurrence of urothelial carcinoma UC in patients who have previously been diagnosed with this bladder cancer. Frequent cystoscopies are the current standard for surveillance but are invasive, costly, and time-consuming. This observational study aims to validate how well these urine tests can identify cancer recurrence compared to cystoscopy and pathology results over multiple visits. Participants include low-, intermediate-, and high-risk patients undergoing routine surveillance for UC recurrence. During up to four consecutive surveillance visits, patients will provide voided urine samples not catheterized for CxBladder testing and central urine cytology. Tissue samples from the original tumor and any recurrences within 12 weeks will be collected for molecular analysis. The study does not provide test results to patients or doctors and follows strict procedures for sample and data collection. Throughout the study, participants will attend four visits for urine sample collection and cystoscopy as part of their usual care. Researchers will measure the tests sensitivity, specificity, predictive values, and negative rates compared to tumor findings confirmed by pathology. The study includes safety and quality oversight to ensure proper sample handling and adherence to guidelines. Participation lasts up to 12 months, during which multiple urine samples and tissue specimens are collected for research purposes.

Researchers are evaluating a master screening protocol called Lung-MAP for patients with previously treated non-small cell lung cancer. This phase IIIII trial aims to develop a genomic screening method for large cancer populations and assign participants to appropriate sub-studies based on specific cancer biomarkers. The goal is to compare new targeted therapies designed to block cancer growth or spread with standard care, including sub-studies for patients not eligible for biomarker-driven treatments. The study involves screening patient specimens to determine eligibility for various biomarker-driven or non-matched sub-studies within the Lung-MAP umbrella protocol. This is a screening study without direct interventions instead, patients are assigned to different treatment sub-studies, each operating independently. The protocol also includes an optional ancillary study evaluating attitudes about the return of somatic mutation findings suggestive of germline mutations. Participants provide tumor tissue for biomarker testing, including molecular profiling and PD-L1 analysis, and may submit fresh biopsies and blood samples for circulating tumor DNA testing. Researchers will monitor screening success rates up to three years and collect patient and physician feedback on genetic findings. Participation involves signing informed consent, providing smoking history, and possibly completing surveys. The study duration and assessments vary depending on sub-study assignment and patient progression.

Researchers are evaluating ways to improve bladder cancer monitoring by replacing some cystoscopy procedures with urine testing in patients with early-stage non-muscle invasive bladder cancer. This randomized phase 2 study involves 240 participants and aims to compare urinary symptoms, discomfort, anxiety, complications, cancer recurrence, and progression among different monitoring approaches. Participants will be assigned to one of three groups frequent cystoscopy, Xpert urine test, or Bladder EpiCheck urine test. The frequent cystoscopy group will have cystoscopy procedures at 6, 12, 18, and 24 months. The Xpert and EpiCheck groups will have urine tests and doctor check-ups at 6 and 18 months, with cystoscopy at 12 and 24 months. The study period for monitoring is 24 months. During the study, participants will complete quality of life questionnaires at 3, 6, 12, 18, and 24 months to assess urinary quality of life. Researchers will monitor urinary symptoms, number of invasive procedures, anxiety, and cancer outcomes. Follow-up includes multiple assessments over two years to evaluate the impact of different surveillance methods on patient well-being and cancer management.

This research focuses on preventing suicide among Veterans who receive acute psychiatric treatment in non-VA settings affiliated with the Department of Veterans Affairs VA. It addresses a critical gap since these Veterans are at high risk of suicide after discharge, yet have not been the main focus of existing VA suicide prevention efforts. The study evaluates whether the VA Brief Intervention and Contact Program VA BIC, a promising suicide prevention strategy tailored to Veterans needs, can reduce suicide risk compared to standard care alone. Participants will be randomly assigned to receive either the VA BIC intervention plus standard care or standard care alone. The VA BIC includes a one-on-one, hour-long educational session on suicide prevention using motivational interviewing techniques, followed by seven regular follow-up contacts to monitor symptoms, review safety plans, and support mental health engagement. Both groups will have access to standard care provided after discharge from non-VA mental health treatment. Veterans aged 18 and older who have had recent suicidal thoughts and received acute psychiatric treatment outside VA settings will be enrolled. Researchers will assess suicidal ideation using the Beck Scale for Suicidal Ideation, mental health care engagement, social connectedness, and suicide attempts at baseline and at 3, 6, and 9 months after enrollment. The study includes safety monitoring and aims to improve understanding of effective suicide prevention for Veterans in community care settings.

Researchers are evaluating a combination therapy approach for adults with newly diagnosed multiple myeloma who are not intended for early autologous transplantation. This phase III trial compares a four-drug combination including daratumumab, bortezomib, lenalidomide, and dexamethasone to a three-drug combination of daratumumab, lenalidomide, and dexamethasone. The study aims to determine whether adding bortezomib improves overall survival and progression-free survival, examining minimal residual disease status and patient-reported outcomes related to neuropathy and quality of life. All participants first receive standard induction therapy with daratumumab administered subcutaneously on scheduled days, oral lenalidomide daily for 21 days per cycle, and oral dexamethasone on specific days, repeated every 28 days for 9 cycles. After induction, patients are randomized to either receive consolidation with bortezomib plus daratumumab, lenalidomide, and dexamethasone followed by maintenance with daratumumab and lenalidomide, or consolidation with daratumumab, lenalidomide, and dexamethasone followed by the same maintenance regimen. Consolidation cycles repeat every 28 days for 9 cycles, and maintenance cycles repeat every 28 days until disease progression or unacceptable toxicity. Participants undergo regular monitoring including imaging with PETCT scans, bone marrow biopsies for minimal residual disease assessment, and laboratory tests throughout induction, consolidation, and maintenance phases. Patient-reported outcomes on neuropathy and quality of life are collected, alongside safety monitoring for adverse events. After completing study treatment, participants are followed every 3 months for up to 2 years, then every 6 months up to 5 years, and annually up to 15 years to evaluate long-term outcomes and survival.