Warwick

This research investigates dry eye disease by evaluating the safety and effectiveness of a fixed-dose combination of lifitegrast and perfluorohexyloctane given twice daily. The study is a 4-week, randomized, double-masked, parallel-group, active-controlled, multicenter trial focusing on improving signs and symptoms of dry eye disease. Participants must have a history of dry eye disease in both eyes for at least six months and meet specific symptom and sign criteria at screening and baseline. Participants will be assigned to one of several groups receiving topical eye drops for four weeks: the fixed-dose combination of lifitegrast and perfluorohexyloctane, lifitegrast alone, perfluorohexyloctane alone, or a vehicle drop without active ingredients. Each treatment is administered as an eye drop twice daily. The study compares these treatments to assess their impact on dry eye disease. Throughout the study, participants will undergo assessments including corneal fluorescein staining to measure changes from baseline at day 29. They will be monitored for adherence and safety, with evaluations of visual acuity and ocular health. The total participation time is approximately four weeks, during which researchers will track changes in dry eye disease signs and symptoms to evaluate treatment effects.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and efficacy of TP-05 in healthy adults who are at high risk of tick exposure and Lyme disease. This Phase 2b randomized, double-blind, placebo-controlled study aims to understand how TP-05 performs compared to a placebo in preventing Lyme borreliosis. The study enrolls adults aged 18 to 70 years who are overtly healthy and able to comply with study procedures. Participants will be randomly assigned to receive either a low dose or high dose of TP-05 or a matching placebo, all administered orally according to a predefined dosing schedule. The study includes a screening period, a treatment period lasting up to 24 weeks, and a safety follow-up period. During treatment, participants will be monitored closely for any adverse effects and signs of Lyme borreliosis. Throughout the study, participants will undergo safety assessments including monitoring of adverse events, clinical laboratory tests, vital signs, physical exams, and electrocardiograms. Researchers will follow participants for approximately 15 months to track safety outcomes and any tick bites or symptoms of Lyme disease. Key measures include changes from baseline in laboratory results, vital signs, and ECG parameters, ensuring thorough safety evaluation over the study course.

Inpatient falls cause serious physical harm and increase healthcare costs, affecting both patients and hospitals. The Centers for Medicare & Medicaid Services (CMS) classify falls with injury as "never events," meaning they are preventable errors that negatively impact hospital safety ratings and reimbursement. Despite evidence showing that fall prevention alarms are not effective, these alarms are still widely used in hospitals. This study aims to reduce the use of these alarms by applying tailored strategies based on education, audit and feedback, and opinion leaders, guided by the Choosing Wisely De-implementation Framework. It will compare different coaching intensities to find effective ways to reduce alarm use in hospital units. The study involves 30 medical or medical-surgical hospital units across the US. These units will be randomly assigned to receive either high-intensity or low-intensity coaching to implement the tailored strategies for reducing fall prevention alarm use. Coaches will train hospital staff in quality improvement and fall prevention practices, customizing their support to each site's needs. This approach may help future efforts to reduce low-value alarm use in other healthcare settings with high fall risks. Participants include stakeholders involved in fall prevention at the participating hospitals. The study will monitor the prevalence of fall prevention alarms and record patient falls monthly over 30 months. Researchers will assess how well the coaching strategies reduce alarm use and improve patient safety. The findings will inform best practices for de-implementing ineffective alarms and may guide broader quality improvement initiatives in healthcare.

Researchers are evaluating whether breast conservation surgery combined with endocrine therapy can achieve a similar rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation surgery followed by breast radiation and endocrine therapy in patients with Stage I, hormone sensitive, HER2-negative breast cancer with an Oncotype recurrence score of 18 or less. This Phase III trial builds on the established role of radiation after lumpectomy, aiming to identify if radiation can be safely omitted in certain low-risk patients to reduce treatment burden and side effects. Participants receive either breast radiation plus endocrine therapy or endocrine therapy alone. Radiation therapy involves external beam radiation to the whole breast with or without a boost, partial breast irradiation, or accelerated partial breast irradiation, starting within 12 weeks after the last breast surgery. Endocrine therapy is given for a minimum of 5 years, with the specific drug choice and schedule determined by the treating physician. Endocrine therapy may begin before, during, or after radiation therapy, depending on the treatment group. Throughout the study, participants undergo regular assessments including imaging such as mammograms or MRI within six months before enrollment, and clinical evaluations to monitor tumor recurrence. The main outcome measured is the time to invasive or non-invasive ipsilateral breast tumor recurrence over five years. Safety, adherence to therapy, and recovery from surgery are also monitored. The total participation period includes at least five years to evaluate long-term recurrence rates.

Researchers are evaluating if adding adjuvant chemotherapy (ACT) to ovarian function suppression (OFS) plus endocrine therapy (ET) improves invasive breast cancer-free survival (IBCFS) compared to OFS plus ET alone. This Phase III trial focuses on premenopausal women with early-stage breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and has a 21-gene recurrence score between 16-25 for node-negative patients or 0-25 for patients with 1-3 positive nodes. The study addresses the need for better treatment options for younger women diagnosed with this type of breast cancer, as younger age is linked to worse outcomes despite standard therapies. Participants receive one of two treatments: either OFS combined with an aromatase inhibitor (AI) for five years or adjuvant chemotherapy followed by the same OFS plus AI regimen. The specific AI and GnRH agonist used, along with their dosing schedules, are chosen by the investigator, commonly including goserelin, leuprolide, or triptorelin administered monthly or every three months. Bilateral oophorectomy may be used instead of ovarian suppression if preferred. Endocrine therapy beyond five years is at the investigator's discretion. During the trial, participants will be closely monitored for invasive breast cancer-free survival over an 11-year period from randomization. Assessments include clinical evaluations, hormone receptor testing, tumor staging, and genetic recurrence scoring prior to enrollment. Safety and effectiveness data will be collected throughout the study, with particular attention to treatment side effects and long-term outcomes. The trial involves detailed eligibility screening and ongoing follow-up to ensure accurate measurement of the study's primary outcome.

Researchers are evaluating surgical and minimally invasive treatments for lumbar spinal stenosis (LSS) by comparing Medicare patients who received the MILD procedure against those who had interspinous process decompression (IPD). The study focuses on outcomes such as the rate of harms related to the initial procedure and the frequency of additional surgical or minimally invasive interventions within 24 months after treatment. Enrollment includes patients treated from January 1, 2017, onward, with continuation until the sponsor decides to stop. The MILD procedure involves percutaneous image-guided lumbar decompression, performed under fluoroscopy through a dorsal approach to partially remove tissue and bone at the affected spinal level. The control group receives the IPD procedure for LSS. Both groups are monitored for a 24-month period post-index procedure using Medicare claims data to track reoperations and any harms. Participants contribute data through Medicare claims without needing prior enrollment or consent, as the study is exempt from IRB oversight. Researchers collect and analyze information on procedure-related harms and subsequent interventions over two years. This approach allows evaluation of long-term safety and effectiveness outcomes for patients treated with either MILD or IPD.

Researchers are evaluating the safety and effectiveness of Phentolamine Ophthalmic Solution in adults who have previously undergone keratorefractive surgery and experience reduced visual acuity in low light conditions. This phase 3 trial compares the effects of Phentolamine Ophthalmic Solution to a placebo to determine if the drug improves night vision. The study focuses on participants who report symptoms like glare, halos, or starbursts that began within two months after their surgery. Participants will be randomly assigned to receive either 0.75% Phentolamine Ophthalmic Solution or a placebo, both administered once daily for two weeks. During this period, participants will visit the clinic weekly for checkups and testing. They will also keep a daily diary to record when they apply the study medication each evening. Throughout the study, participants will undergo vision tests to measure changes in visual acuity under mesopic (low light) conditions. The main outcome is the percentage of participants who gain at least 15 letters (equivalent to 3 lines) improvement in vision at day 15 compared to the start. Researchers will monitor safety and collect data on any side effects. Participation involves regular clinic visits, vision assessments, and adherence tracking over the two-week treatment period.

Researchers are evaluating the safety and effectiveness of DAS181 for treating lower respiratory tract parainfluenza virus (PIV) infection in immunocompromised patients. This Phase III study includes a sub-study enrolling patients with severe COVID-19. Participants are grouped based on age, type of viral infection, and immune status to better understand treatment effects across different patient populations. The study involves treatment with DAS181, delivered as a nebulized drug once or twice daily for 7 or 10 days depending on the cohort. There is also a placebo group receiving nebulized placebo on the same schedule. Dose adjustments for DAS181 depend on the participant's weight in certain groups. The sub-study specifically investigates DAS181 administered twice daily in patients with severe COVID-19. Treatment is carefully monitored and tailored by cohort criteria, including age and viral infection type. Participants will be closely followed with various assessments including oxygen usage, respiratory virus detection, and lung imaging. The main outcomes measured are the percentage of participants who return to breathing room air by day 28 and improvement in COVID-19 clinical status by day 14 for the sub-study. Safety assessments include liver function tests and monitoring for serious infections. The study requires informed consent and adherence to protocol procedures, with a total participation duration covering treatment and follow-up periods.

Researchers are evaluating the effectiveness and safety of benralizumab as an additional treatment for people aged 12 to 75 with uncontrolled eosinophilic asthma who are already using medium-dose inhaled corticosteroids combined with long-acting beta2-agonists (ICS-LABA). The study compares this approach to the usual care of increasing inhaled therapy to high-dose ICS-LABA. This is a global, phase 3b, randomized, double-blind, active-controlled trial involving participants with a history of eosinophilic asthma. Participants receive either benralizumab 30 mg by subcutaneous injection every 4 weeks for the first three doses and then every 8 weeks, alongside their medium-dose ICS-LABA treatment, or they receive a placebo injection with an increased high-dose ICS-LABA treatment. The study includes a run-in period to monitor compliance with usual asthma treatment and aims to assess adding benralizumab versus stepping up inhaled therapy. During the study, researchers monitor asthma control, lung function, and exacerbations over 48 weeks. Participants complete asthma diaries to track medication adherence and symptoms. The main outcome measured is the annual rate of asthma exacerbations. Safety and adverse events are also closely followed throughout the study period.

This research aims to compare the effects of usual care including regional radiation therapy with no regional radiation therapy in women with low-risk breast cancer. It focuses on patients with node positive breast cancer or T3N0 disease who typically receive endocrine therapy and possibly chemotherapy to prevent cancer recurrence. The study examines whether skipping regional radiotherapy still effectively prevents breast cancer from returning, potentially reducing unnecessary treatment and side effects. Participants will be divided into two groups: one receiving radiotherapy to the breast/chest area and surrounding lymph nodes, and the other receiving no regional radiotherapy. The study evaluates standard treatments, ensuring radiation therapy starts within specific time frames after surgery or chemotherapy. Treatments include breast-conserving surgery or mastectomy, along with endocrine therapy planned for at least five years. During the study, researchers will monitor breast cancer recurrence-free intervals over approximately 9.5 years. Participants will undergo regular assessments to track cancer status, side effects, and overall health. The study includes quality of life questionnaires for some patients and requires ongoing follow-up to document treatment effects, adverse events, and long-term outcomes.