Coventry

Researchers are evaluating two different methods of pacing the heart in patients with slow heart rates (bradycardia). This multi-center randomized controlled trial, called PROTECT-HF, aims to compare the standard right ventricular pacing approach with a newer physiological pacing technique, which includes His bundle and left bundle area pacing. The study will enroll 2600 patients to assess differences in outcomes related to heart function and survival. Participants will be randomly assigned to receive either right ventricular pacing or physiological pacing through pacemaker implantation. The physiological pacing method may involve His bundle pacing or left bundle pacing, with biventricular pacing used if these are not possible. Both treatments will be performed at participating centers, with patients and outcome assessors blinded to the treatment allocation. A subgroup of 500 patients will also take part in an optional echocardiographic sub-study to observe heart changes over 24 months. During the study, participants will be monitored from the time of consent for up to 78 months. Evaluations will occur at the start and every six months afterward to track mortality and heart failure-related health events. Researchers will gather data on heart function, treatment effects, and safety. The main analysis will consider all patients as originally assigned, and additional analysis will assess those who received the assigned treatment.

Researchers are evaluating whether an investigational drug called OHB-607 can prevent Bronchopulmonary Dysplasia (BPD), a common chronic lung disease, in extremely premature infants. The study compares infants receiving OHB-607 alongside standard neonatal care to those receiving standard care alone to reduce the burden of this lung condition. This is a Phase 2b, multicenter, randomized, open-label study focused on safety and clinical efficacy. Participants will receive an intravenous infusion of OHB-607 from birth until reaching a postmenstrual age (PMA) of 29 weeks and 6 days. The study includes two arms: one group receives the investigational drug plus standard care, while the other group receives only standard neonatal care. The treatment period ends at 29 weeks plus 6 days PMA, after which infants are monitored. Throughout the study, researchers will track the incidence of severe BPD or death up to 36 weeks PMA, whichever occurs first. Assessments will include clinical evaluations and monitoring for safety and any side effects. The study also involves long-term follow-up to observe the infants' health outcomes beyond the treatment period. Participation involves consent from parents and collection of birth and medical history information.

Researchers are investigating sacituzumab tirumotecan (MK-2870) alone or combined with other treatments to treat certain gastrointestinal cancers. These include colorectal cancer that cannot be removed by surgery or has spread, advanced pancreatic ductal adenocarcinoma, and biliary tract cancer. The study aims to understand the safety and tolerability of sacituzumab tirumotecan and measure how many participants respond to the treatment by having their cancer shrink or disappear. Participants may receive sacituzumab tirumotecan by intravenous infusion alone or with other anticancer drugs such as fluorouracil (5-FU), leucovorin or levoleucovorin, cisplatin, and pembrolizumab. Rescue medications like diphenhydramine, H2 receptor antagonists, acetaminophen, dexamethasone, and a steroid mouthwash are given to prevent infusion reactions and oral side effects. Supportive care treatments for side effects, including antidiarrheal and antiemetic agents, are allowed throughout the study. During the study, researchers monitor participants for dose-limiting toxicities within about 4 weeks and track adverse events, treatment discontinuations, and tumor response over up to approximately 63 months. Assessments include safety evaluations and measuring cancer response using standardized criteria. This long-term follow-up helps evaluate both the effectiveness and safety of the treatments being studied.

Researchers are evaluating the effect of vipoglanstat on reducing non-menstrual pelvic pain related to endometriosis in women. This phase 2 trial focuses on women who have moderate to severe pain caused by endometriosis, aiming to see how well vipoglanstat works compared to a placebo. The study is designed to measure changes in pain over a period of about four months. Participants in this trial will receive either vipoglanstat capsules or matching placebo capsules taken orally for approximately four menstrual cycles during the treatment period. The study is randomized and double-blind, meaning neither participants nor researchers know who receives the active drug or placebo until the study ends. Two different doses of vipoglanstat are being tested to assess safety and effectiveness. During the study, women will be monitored for changes in their endometriosis-related non-menstrual pelvic pain, with the primary measure being the percentage of participants who meet a specific pain response criterion from the start of the study to the fourth month of treatment. The trial includes careful tracking of symptoms and safety over the treatment duration to evaluate how well vipoglanstat manages pain in this population.

This trial investigates the safety and effectiveness of rilvegostomig combined with fluoropyrimidine and trastuzumab deruxtecan (T-DXd) compared to trastuzumab, chemotherapy, and pembrolizumab in adults with HER2-positive locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 with a combined positive score of 1 or higher. Additionally, rilvegostomig combined with trastuzumab and chemotherapy is studied separately to understand each component's contribution. This Phase 2, randomized, open-label, global study is conducted at 200-250 sites in about 25 countries. Participants are randomly assigned to one of three arms: Arm A receives rilvegostomig, fluoropyrimidine, and T-DXd; Arm B receives trastuzumab, chemotherapy, and pembrolizumab; Arm C receives rilvegostomig, trastuzumab, and chemotherapy. Treatments are administered mostly by intravenous infusion every three weeks, with capecitabine given orally twice daily. The study compares these treatment regimens to evaluate their effects on the cancer. Throughout the study, participants undergo assessments including tumor measurements, organ function tests, and heart function evaluation to ensure safety and monitor disease progression. The main outcomes measured are progression-free survival and overall survival for up to approximately six years. Researchers will also monitor adverse events and overall health status during and after treatment.

Researchers are investigating treatments for patients with hormone receptor-positive (HR-positive), HER2-negative early-stage breast cancer who are at higher risk of relapse after surgery within the last five years. This phase II, open-label study uses a biomarker-driven approach to monitor minimal residual disease (MRD) by analyzing circulating tumor DNA (ctDNA) in blood samples. The study includes a pre-screening phase, a molecular follow-up phase with ctDNA surveillance, and an interventional treatment phase, aiming to identify patients at molecular relapse and evaluate whether early treatment can improve outcomes. Participants first enter a ctDNA surveillance phase where tumor tissue and blood samples are collected to create individualized mutation panels. Blood is tested every three months during the first year and every six months thereafter. If ctDNA is detected, patients may enter one of four treatment arms: standard treatment followed by change, giredestrant alone, giredestrant combined with abemaciclib, or giredestrant combined with inavolisib. LHRH agonists are given as appropriate for men and premenopausal women. Treatment dosing and schedules are defined, including special dosing for certain kidney function levels. The study allows arm expansions based on ctDNA response criteria. Throughout the study, patients undergo regular ctDNA assessments to monitor treatment response. Safety and disease progression are tracked with scans and clinical evaluations. After treatment, a follow-up period collects survival and new therapy information every three months until study end. The primary outcome is measuring a decrease or clearance of baseline ctDNA three months after starting treatment. Total enrollment includes 976 patients for surveillance, with 40 allocated to treatment arms initially, and potential expansion based on results.

Researchers are evaluating HER3-DXd monotherapy in adults with locally advanced unresectable or metastatic solid tumors who have been previously treated with at least one systemic anticancer therapy. This phase 2 proof-of-concept study includes participants with various cancers such as melanoma, squamous cell carcinoma of the head and neck, HER2-negative gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, lung cancer, and breast cancer. The study aims to assess the safety, tolerability, efficacy, and pharmacokinetics of HER3-DXd, as well as the relationship between HER3 protein expression in tumor tissue and treatment response. Participants receive HER3-DXd as an intravenous infusion at a dose of 5.6 mg/kg every 21 days on Day 1 of each cycle. The study is organized into multiple cohorts based on tumor type, with treatment continuing until disease progression, unacceptable toxicity, withdrawal, or other specified reasons. HER3 protein expression and its association with treatment outcomes are also investigated. Throughout the study, participants undergo regular assessments including tumor response evaluations according to RECIST v1.1 criteria, radiographic imaging, and laboratory tests. For prostate cancer participants, prostate-specific antigen (PSA) levels are monitored each cycle. Safety and tolerability are closely observed up to approximately 27 months. Participants provide tumor tissue samples either from archival or fresh biopsies before treatment initiation. The overall study duration includes screening, treatment cycles, and follow-up for disease progression or other outcomes.

Researchers are studying the immune response and safety of mRNA-1018-H5, a pandemic influenza vaccine, in adults aged 18 years and older. The trial aims to assess how well two doses of this vaccine trigger antibody production and to monitor any side effects or reactions. This is a Phase 3, randomized, observer-blind, placebo-controlled study focused on the influenza virus. Participants will receive either the mRNA-1018-H5 vaccine or a placebo, both provided as sterile liquid injections. The study involves two doses and includes detailed monitoring for immune response and side effects after vaccination. The trial compares the vaccine to a placebo to evaluate its immunogenicity and safety. During the study, individuals will undergo medical evaluations including physical exams and pregnancy testing if applicable. Researchers will measure antibody levels at Day 43 and record any local or systemic reactions up to Day 29 after injections, as well as any adverse events up to Day 205. The study tracks serious and medically-attended adverse events to ensure careful safety monitoring throughout the participation period.

Researchers are studying the effects of DMX-200 (repagermanium), a drug that blocks a receptor involved in inflammation, in people with focal segmental glomerulosclerosis (FSGS) who are also taking an angiotensin II receptor blocker (ARB). This Phase 3 trial aims to assess the safety and effectiveness of DMX-200 compared to placebo over 104 weeks in adults and adolescents aged 12 to 17 years. Following the initial study, an open-label extension will evaluate long-term safety and benefits for up to two more years. Participants will be randomly assigned to receive either DMX-200 at 120 mg twice daily or a placebo, while continuing their ARB treatment. The study includes a screening and qualification period lasting 6 to 14 weeks, a 104-week double-blind treatment phase, and a 4-week follow-up after treatment. Those completing this phase may enter the open-label extension for an additional minimum of 104 weeks, with another 4-week follow-up period, making the total study duration about 230 weeks. During the trial, participants will undergo regular assessments including urine protein and creatinine testing, kidney function monitoring by estimated glomerular filtration rate (eGFR), and safety evaluations. The main outcomes measured are changes in proteinuria, kidney function slope up to week 104, and long-term safety through week 216. Safety will be closely monitored throughout both the double-blind and extension periods to understand the drug's effects over time.

Researchers are evaluating XTMAB-16 in a phase 1b/2 study involving patients with pulmonary sarcoidosis, a condition affecting the lungs and sometimes other parts of the body. This study aims to assess the safety and effects of multiple doses of XTMAB-16 compared to a placebo in patients with this condition, including those with or without extrapulmonary manifestations. The trial follows guidelines for diagnosing pulmonary sarcoidosis and requires participants to have a certain level of breathing difficulty and ongoing treatment with corticosteroids or other specified immunosuppressive medications. Participants receive infusions of either XTMAB-16 or a placebo. The study includes a multiple ascending dose phase and proof of concept evaluation. During the screening and treatment periods, participants must avoid grapefruit products and undergo tests to confirm they do not have COVID-19. Background therapies are maintained stable when possible, and corticosteroid tapering is managed under investigator supervision. The total study duration for the primary outcome assessment is 20 weeks in part A. Throughout the study, participants undergo regular assessments including monitoring for adverse events, laboratory tests, physical exams, and vital signs. The primary outcome measured is the rate of adverse events, including serious and dose-limiting toxicities and events of special interest. Safety monitoring is continuous, and participants must provide informed consent and be able to comply with study requirements. The trial excludes individuals with certain health conditions, recent treatments, or infections to ensure safety and accurate evaluation of the study drug.