Portsmouth

Researchers are evaluating the effectiveness and safety of a combination inhaler containing fluticasone propionate and albuterol sulfate, delivered via a multidose dry powder inhaler with an electronic module, in participants aged 12 years and older with asthma. This Phase 3 trial aims to compare this combination treatment to fluticasone propionate alone, albuterol sulfate alone, or a placebo inhaler. The study also assesses different dosing schedules, safety, tolerability, and pharmacokinetics of these inhalers. Participants will be randomly assigned to one of four groups receiving either the combination inhaler, fluticasone propionate inhaler, albuterol sulfate inhaler, or placebo, all with integrated electronic modules. Treatments are administered over a 4-week period with dosing four times daily. Pharmacokinetic assessments will be conducted after a single dose administration. The study is double-blind and placebo-controlled, with a parallel group design. Throughout the approximately 10-week study period, including screening and treatment, participants will undergo evaluations including lung function tests measuring forced expiratory volume in one second FEV1, asthma control questionnaires, and safety assessments. Researchers will monitor treatment-emergent adverse events and measure blood concentrations of the inhaled drugs. The study includes electronic monitoring of inhaler use and collects data at baseline, during treatment, and at week 4, with follow-up to assess efficacy and safety.

Researchers are evaluating a new treatment approach for children and young adults newly diagnosed with acute myeloid leukemia AML, including those with and without FLT3 gene mutations. The trial compares standard chemotherapy using daunorubicin, cytarabine, and gemtuzumab ozogamicin to therapy with CPX-351, a liposome-encapsulated form of daunorubicin and cytarabine, andor the drug gilteritinib which may block abnormal FLT3 gene function. The study aims to understand which treatment works better and to monitor heart function changes during and after therapy. Participants are assigned to different treatment groups based on their risk and FLT3 mutation status. Treatments include various chemotherapy regimens delivered intravenously and intrathecally, with some groups receiving CPX-351 and others receiving standard drugs. Patients with FLT3 mutations receive additional oral gilteritinib for extended periods, including maintenance therapy up to one year. Hematopoietic stem cell transplantation is also part of the treatment for some high-risk patients following chemotherapy courses. During the study, participants will undergo multiple assessments including blood tests, bone marrow biopsies, imaging scans, and neuropsychological testing to monitor leukemia status and treatment effects. Cardiac function is closely followed using echocardiography and biomarkers. Patient outcomes such as event-free survival, overall survival, minimal residual disease, relapse rates, and treatment safety are tracked for up to three years. The total study participation may extend over several years with ongoing evaluations.

Researchers are evaluating whether adding immunotherapy drugs brentuximab vedotin and nivolumab to the standard treatment of chemotherapy with or without radiation improves survival for patients aged 5 to 60 with early stage classical Hodgkin lymphoma. This phase III trial compares progression-free survival and overall survival between the standard therapy and the immunotherapy-enhanced approach, as well as patient-reported outcomes and long-term side effects. Participants initially receive two cycles of ABVD chemotherapy every 28 days and then undergo imaging to classify their early response. Based on risk level and response, patients are assigned to one of eight treatment arms that include either continuing standard chemotherapy, receiving immunotherapy drugs, or combinations with involved-site radiation therapy. Treatments are delivered intravenously or orally in cycles lasting 28 days. Imaging and blood samples are collected throughout the trial. Participants are monitored regularly with PET scans, CT or MRI imaging, and blood tests. Follow-up visits occur every 3 months in the first year, then every 6 months for years two and three, and annually up to 12 years from registration. Researchers assess survival outcomes, adverse events, patient-reported symptoms and quality of life, and metabolic tumor burden. Long-term effects such as cardiovascular and pulmonary health are also evaluated using questionnaires and clinical assessments.

This trial investigates monitoring and treatment options for patients with low risk and standard risk metastatic germ cell tumors, which are cancers that start in the cells that produce sperm or eggs. The study aims to find out if active surveillance after surgical removal of low risk tumors can maintain high survival rates, and whether carboplatin or cisplatin chemotherapy works better for treating standard risk tumors in children, adolescents, and young adults. Patients with low risk tumors undergo observation after surgery and may transfer to a standard risk treatment arm if the tumor recurs. Those with standard risk tumors are randomly assigned to receive one of two chemotherapy regimens one containing carboplatin, bleomycin, and etoposide, or the other containing cisplatin, bleomycin, and etoposide. Treatments are given intravenously in cycles every 21 days for up to 3 or 4 cycles depending on the group. Throughout the study, patients have imaging scans, blood tests, tumor biopsies, and pulmonary function tests to monitor response and side effects. Participants are followed closely during treatment and afterward with regular check-ups including CT, MRI, and chest X-rays, as well as blood sample collections. Follow-up visits occur every 2 months for the first year, then every 3-6 months up to 2 years, every 6 months for years 3 to 5, and annually up to 10 years. Researchers measure overall survival, event-free survival, hearing loss, body composition, tumor markers, and patient-reported outcomes related to hearing and neuropathy. This long-term monitoring helps assess the effects and safety of chemotherapy and surveillance strategies.

Researchers are evaluating how different types of casts affect satisfaction and pain in children with upper or lower extremity fractures. The study compares plain white casts, colored casts chosen by the child, and casts decorated with custom art like drawings and glitter. It aims to understand how cast customization influences patient and parent satisfaction and perceived pain during healing. Participants will be randomly assigned to one of three groups receiving a neutral white cast, a cast wrapped in the participants chosen color, or a cast with custom artwork. The casts are applied either in the emergency department or during follow-up visits, including after surgery if needed. The length of casting depends on the fracture type and healing progress monitored through radiographs. Children will be assessed at multiple time points after injury, including 0-2 weeks, 4-6 weeks, and 8-12 weeks if needed. Researchers will collect satisfaction scores using a visual analog scale and pain data using a pediatric pain questionnaire. Clinical and radiographic data will also be reviewed to monitor healing. The total participation duration is based on the healing time required for the fracture.

Researchers are evaluating a treatment approach for early-stage hormone-sensitive, HER-2 negative breast cancer with an Oncotype recurrence score of 18 or less. This Phase III trial compares breast conservation surgery with endocrine therapy alone against breast conservation surgery with both radiation and endocrine therapy. The goal is to see if skipping radiation after lumpectomy is not worse in preventing cancer recurrence in the same breast. Participants will be randomly assigned to one of two groups. One group will receive radiation therapy to the breast plus at least five years of endocrine therapy with drugs such as Tamoxifen, Anastrozole, Letrozole, or Exemestane. The other group will receive endocrine therapy only for at least five years without radiation. Radiation must start within 12 weeks of surgery if assigned. Endocrine therapy dosing and schedule are determined by the treating doctor. During the study, participants will have regular follow-ups up to five years to monitor cancer recurrence in the breast and elsewhere, survival, and breast preservation. Assessments will include clinical exams, imaging like mammograms or MRI, and pathology reviews. The main outcome is time to invasive or noninvasive breast tumor recurrence within five years. Some measures will continue through an average of 15 years, including breast conservation rates. Safety and overall health will be monitored throughout and after treatment.

Researchers are evaluating the addition of dinutuximab to standard treatments for children with newly diagnosed high-risk neuroblastoma, a type of cancer that affects nerve tissue. This phase III trial compares standard chemotherapy and surgery to chemoimmunotherapy, which combines chemotherapy with dinutuximab, an antibody aimed at helping the immune system target cancer cells. The study also explores how these treatments affect survival, response rates, side effects, tumor markers, and quality of life. Participants receive multiple cycles of induction chemotherapy with drugs like cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. They are randomly assigned to either standard chemotherapy alone or chemotherapy combined with dinutuximab. After initial treatment cycles, tumor response is assessed to guide further therapy patients with good responses proceed to high-dose chemotherapy with stem cell transplants and radiation, followed by post-consolidation immunotherapy with dinutuximab and isotretinoin. Those with poor responses receive additional chemoimmunotherapy during an extended induction phase. Throughout the study, participants undergo blood and urine tests, heart scans, bone marrow biopsies, and various imaging scans including CT, MRI, and specialized PET scans. The research team monitors treatment effects, tumor markers, and quality of life over time. After completing treatment, patients are followed regularly for up to 10 years to assess long-term outcomes and side effects, with the main goal of measuring event-free survival up to three years.

This research aims to evaluate the efficacy and safety of rimegepant compared to a placebo as a preventive treatment for migraine in children and adolescents aged 6 to under 18 years with episodic migraine. It focuses on reducing the frequency of migraine days over a 12-week period, particularly in young patients who experience mild to moderate disruption in daily activities due to migraine. The study is designed as a Phase 3 randomized, double-blind trial to assess this preventive approach. Participants will be randomly assigned to receive either rimegepant at doses of 75mg or 50mg two 25mg orally disintegrating tablets or a matching placebo with the same dosing options. The treatment phase lasts 12 weeks in a double-blind manner, followed by a safety and tolerability evaluation over a total of 72 weeks. The study includes sequential treatment with careful monitoring of migraine frequency and medication use during this period. Throughout the trial, participants will be monitored for migraine days per month, reduction in migraine frequency, and quality of life as measured by the Pediatric Quality of Life Inventory PedsQL. Researchers will also assess the use of acute migraine medications, hepatic-related adverse events, and overall safety. The primary outcome focuses on the change in migraine days during the 12-week treatment phase. Participants adherence and safety will be tracked throughout the treatment and follow-up periods, lasting up to nearly 10 years until study completion.

Researchers are evaluating if adding inotuzumab ozogamicin to standard chemo-immunotherapy after initial induction improves outcomes for children and young adults with High-Risk B-cell Acute Lymphoblastic Leukemia B-ALL. The study also includes patients with Mixed Phenotype Acute Leukemia MPAL and B-lymphoblastic lymphoma B-LLy receiving similar therapy. This phase III trial aims to understand whether this addition maintains or improves survival and treatment response while evaluating side effects and quality of life. Participants first complete induction therapy involving multiple chemotherapy drugs and steroids based on age, followed by randomization into one of two groups if they have CD22-positive High-Risk B-ALL. One group receives a modified chemotherapy regimen including inotuzumab ozogamicin, replacing parts of consolidation and delayed intensification phases. The other group receives the full chemo-immunotherapy regimen without inotuzumab. Patients with MPAL and B-LLy receive treatment according to specified arms with similar chemotherapy combinations adjusted for their condition. Treatments involve intravenous, intrathecal, and oral medications, as well as radiation therapy for certain cases. Throughout the study, participants undergo various assessments including blood samples, bone marrow tests, and imaging scans. Side effects and health-related quality of life are monitored using patient-reported outcomes. Adherence to oral chemotherapy and immune system effects are also evaluated. After completing treatment, participants are followed regularly to monitor survival, relapse, and long-term health up to five years. The study also explores social determinants of health and their impact on outcomes.

Researchers are comparing how long pain relief lasts between two types of local anesthetic combinations used during erector spinae plane blocks for patients undergoing mastectomy surgery for breast cancer. This trial aims to see if adding dexmedetomidine to bupivacaine provides longer or more effective pain control than using liposomal bupivacaine with bupivacaine alone. The study measures differences in pain relief duration and the amount of opioid pain medication needed after surgery. Participants will receive an erector spinae plane block guided by ultrasound performed by the Acute Pain Service team. Patients are randomly assigned by month to receive either bupivacaine 0.25% with liposomal bupivacaine or bupivacaine 0.25% with dexmedetomidine. The local anesthetic is delivered using a needle placed under direct visualization into the erector spinae plane, with doses adjusted by patient weight and surgical side. All patients receive 10 mg intravenous dexamethasone after anesthesia induction. During the hospital stay, pain scores and opioid use in morphine equivalents are recorded every 6 hours starting in the recovery area until discharge. After discharge, participants are contacted at 72 hours to report daily pain scores and opioid tablet use since leaving the hospital. The primary outcome is the density and duration of pain relief over 96 hours, while secondary measures include total oral opioid consumption during the same period.