Hartford

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are evaluating two forms of buprenorphine treatment for Veterans with moderate to severe opioid use disorder (OUD). This Phase 4, open-label, randomized controlled trial aims to compare a 28-day injectable subcutaneous buprenorphine formulation at a target dose of 300 mg with the standard daily sublingual buprenorphine dose ranging from 4 to 32 mg. The study will recruit 952 Veterans over seven years and follow them actively for 52 weeks, with additional passive follow-up via medical records for up to 10 years. The study also explores secondary outcomes including other substance use, overdose incidents, infections like HIV and hepatitis, incarceration, quality of life, mental health symptoms, housing, dental health, and cost-effectiveness. Participants will begin induction on daily sublingual buprenorphine using standard guidelines to reach a target dose between 4 and 32 mg within 45 days. After reaching this dose, participants are randomly assigned to either continue daily sublingual buprenorphine with naloxone, prescribed in 28-day take-home supplies, or receive monthly injectable buprenorphine administered in the clinic. Both treatment groups have visits at weeks 1, 2, 3, and 4 post-randomization, then every two weeks until week 52, with medication management provided at each visit. During the study, participants will provide self-reports of opioid abstinence and undergo urine drug screenings every two weeks. Medication adherence and retention in treatment are tracked approximately every four weeks. After the active 52-week period, participants will be followed passively through electronic medical records for up to 10 years to monitor long-term outcomes. This comprehensive approach aims to assess the effectiveness and safety of these treatments for opioid use disorder in Veterans.

Researchers are evaluating the effects of adding cemiplimab, an immunotherapy drug that blocks the PD-1 pathway to help the immune system attack tumor cells, to the usual treatment of docetaxel and ramucirumab in patients with stage IV or recurrent non-small cell lung cancer. This phase II/III Expanded Lung-MAP trial compares cemiplimab combined with docetaxel and ramucirumab versus docetaxel and ramucirumab alone, aiming to improve treatment outcomes in patients who previously received platinum chemotherapy and immunotherapy but developed resistance or disease progression. Participants are randomly assigned to one of two treatment arms. In Arm I, patients receive dexamethasone orally twice daily on days 0-2, ramucirumab and docetaxel intravenously on day 1 of each 21-day cycle. In Arm II, patients receive the same treatments plus cemiplimab intravenously on day 1 of each cycle. Treatment cycles continue every 21 days until disease progression or unacceptable side effects occur. Throughout the study, patients undergo regular blood sample collection and imaging scans such as CT or MRI to monitor disease status. During the study, participants are closely monitored with scans, blood tests, and physical exams to assess overall survival and other outcomes like progression-free survival, response rates, and treatment safety. Researchers also collect blood samples for future molecular studies. After completing treatment, patients are followed up every 3 to 6 months for up to 3 years to track long-term survival and health status. The study measures overall survival from randomization to death from any cause, assessed up to 3 years.

Researchers are evaluating the effect of adding chemotherapy to immunotherapy (pembrolizumab) compared to using immunotherapy alone in treating older adults aged 70 and above with advanced non-small cell lung cancer (stage IIIB-IV). This phase III trial aims to determine if combining chemotherapy with pembrolizumab improves overall survival and other outcomes like progression-free survival, response rates, toxicity, and quality of life in this vulnerable patient group. Participants are randomly assigned to one of two treatment groups. In the immunotherapy-alone group, patients receive pembrolizumab intravenously every 21 days for four cycles, followed by maintenance pembrolizumab every 21 or 42 days for up to two years if there is no disease progression or unacceptable side effects. In the combination group, patients receive pembrolizumab plus a chemotherapy regimen chosen by their doctor, including drugs such as pemetrexed, carboplatin, nab-paclitaxel, or paclitaxel, given intravenously on specific schedules for four cycles, followed by the same pembrolizumab maintenance. Imaging scans like MRI, CT, and PET are performed at baseline and throughout the study. During the study, participants undergo various assessments including imaging scans, laboratory tests, and questionnaires to evaluate treatment effects, side effects, and quality of life. Researchers monitor overall survival for up to five years from randomization, with follow-up visits every three months for the first two years and every six months thereafter until five years. Additional exploratory analyses include safety, tolerability, and correlations with gut microbiome and geriatric assessments to better understand treatment outcomes in this population.

Researchers are conducting a prospective observational cohort study to better understand how to safely and effectively remove large polyps that can lead to colorectal and duodenal cancer. This study follows previous research primarily from an Australian group and aims to see if those findings apply to a broader population. It continues an earlier randomized trial while including patients who might not have qualified for that trial, allowing for a wider range of resection techniques and better representation of typical patients undergoing large polyp removal. The study enrolls patients undergoing upper endoscopy or colonoscopy who have large colon polyps (20 mm or bigger) or duodenal polyps (10 mm or bigger). Since this is an observational study, no specific interventions are assigned, but patients receive endoscopic resection according to usual care. The study complements ongoing randomized trials by including additional patients and techniques, helping to gather more comprehensive data on outcomes. Participants are monitored during and after their procedures to assess key outcomes such as the completeness of polyp removal during the procedure, the occurrence of severe complications within 14 days after the procedure, and polyp recurrence up to five years later at their next surveillance colonoscopy. This approach helps evaluate both the immediate and long-term safety and effectiveness of endoscopic polyp removal in a real-world setting.

Researchers are conducting a double-blind, randomized, placebo-controlled trial to evaluate glecaprevir/pibrentasvir (GLE/PIB), a direct-acting antiviral originally approved for hepatitis C virus (HCV) treatment, for improving symptoms of posttraumatic stress disorder (PTSD) in patients without HCV. The study aims to determine the effectiveness of GLE/PIB in reducing PTSD symptoms, enhancing patient functioning, and assessing its safety and tolerability in this new context. Participants will be assigned to receive either GLE/PIB or a placebo that looks identical to the active drug. The trial includes 92 patients diagnosed with PTSD who meet specific eligibility criteria. Treatment effects will be compared by measuring changes from baseline in PTSD symptom scores using the Clinical Administered Post-Traumatic Stress Disorder Scale version 5 (CAPS-5) after eight weeks of therapy. During the study, participants will undergo evaluations including PTSD symptom assessments and monitoring for any side effects or adverse reactions. Researchers will also track functional improvements and overall safety throughout the trial. The total participation includes baseline assessment, treatment over eight weeks, and follow-up evaluations to document symptom changes and tolerability.

Researchers are studying the use of the CxBladder Monitor and Monitor+ urine tests to detect recurrence of urothelial carcinoma (UC), a type of bladder cancer. The study involves patients who have previously been diagnosed with UC and are undergoing routine cystoscopy surveillance, which is invasive and costly. This research aims to validate how well these urine tests perform compared to the standard cystoscopy and pathology confirmation over multiple visits. Participants will provide urine samples at four consecutive surveillance visits, which will be tested using the CxBladder Monitor and Monitor+ assays along with central urine cytology. In addition, tumor tissue samples from the initial and any recurrent UC tumors will be collected when available to analyze genetic markers associated with bladder cancer risk. The test results will not be shared with patients or their doctors during the study. Throughout the study, researchers will collect clinical data and biological samples to assess test performance measures such as sensitivity, specificity, and predictive values. The study will follow participants over these four visits, ensuring sample collection and data recording follow good clinical practice. The total participation time spans these surveillance visits, focusing on validating a less invasive method for bladder cancer monitoring.

Researchers are evaluating a screening and multi-sub-study randomized phase II/III trial called Lung-MAP, designed for patients with previously treated non-small cell lung cancer. The trial aims to establish a genomic screening method to assign patients to biomarker-driven or non-matched sub-studies. Depending on the cancer biomarker type, participants may receive new targeted cancer therapies or combinations compared to standard care, with the goal of approving new treatments. An optional ancillary study explores patient and physician attitudes about returning genetic findings related to germline mutations. The study involves testing patient specimens to determine eligibility for various sub-studies under the Lung-MAP protocol. Patients undergo screening to analyze tumor tissue and blood samples for biomarkers including PD-L1 and c-MET. Those requiring a fresh biopsy also submit blood for circulating tumor DNA testing. Sub-study assignment depends on the molecular profile results. This screening process includes both patients progressing after prior therapy and those pre-screened before progression on current treatment. Participants provide informed consent and tumor tissue that meets quality standards for testing. Researchers collect clinical data including smoking history and performance status. Outcomes focus on screening success, such as adequate tissue submission and matching to biomarker-driven sub-studies, tracked for up to three years. The study also monitors patient and physician knowledge and preferences regarding genomic findings. Participation duration varies based on screening and sub-study assignment.

Researchers are evaluating whether monitoring bladder cancer can be improved by replacing some invasive cystoscopy procedures with urine testing in patients with early-stage non-muscle invasive bladder cancer. This phase 2 trial aims to compare urinary symptoms, discomfort, procedure frequency, anxiety, complications, cancer recurrence, and progression across different monitoring methods. The study includes three groups: one group will have frequent cystoscopy procedures at specified times over two years, while the other two groups will use urine tests (Xpert bladder cancer urine test or Bladder EpiCheck urine test) combined with fewer cystoscopy procedures at 12 and 24 months. Patients in the urine test groups will have urine tests and medical check-ups at 6 and 18 months, reducing the number of invasive cystoscopies needed. The study period spans 24 months. Participants will be assessed using the Quality of Life Questionnaire for Non-Muscle Invasive Bladder Cancer at multiple points (3, 6, 12, 18, and 24 months). Researchers will monitor symptoms, cancer recurrence, and quality of life closely throughout the study. Study visits include urine testing, cystoscopy procedures, medical check-ups, and questionnaires to evaluate urinary quality of life, safety, and cancer control over two years.

This research focuses on preventing suicide among Veterans who receive acute psychiatric treatment in non-VA community care settings, a group at high risk of suicide but not specifically targeted by current VA suicide prevention efforts. The study evaluates a promising intervention called the VA Brief Intervention and Contact Program (VA BIC) designed to reduce suicide risk and improve social connectedness and treatment engagement after discharge from non-VA mental health care. Participants will be randomly assigned to receive either the VA BIC intervention plus standard care or standard care alone. The VA BIC intervention includes a personalized one-hour educational session on suicide prevention using motivational interviewing techniques, followed by seven regular follow-up contacts where a trained mental health provider monitors symptoms, treatment adherence, and safety, and helps promote well-being. Standard care is provided to all participants upon discharge from non-VA treatment, with VA staff following usual risk mitigation procedures. Up to 120 Veterans aged 18 and older who have received acute psychiatric care in VA-affiliated non-VA settings in Northern New England will participate. Suicidal thoughts, mental health care engagement, social connectedness, and suicidal behavior will be assessed at baseline and again at three, six, and nine months. The study aims to determine if VA BIC plus standard care leads to reduced suicidal ideation and improved engagement and connectedness compared to standard care alone.