Clinical trials

Evaluation of the Effect of metamizole (Optalgin®) on Anti-Xa Levels in Oncology Patients Receiving Direct Oral Anticoagulants (DOACs)

This multicenter, prospective, randomized non inferiority trial, conducted at four Israeli hospitals, will evaluate whether a relaxed surveillance strategy after piecemeal endoscopic mucosal resection (pEMR) of large non pedunculated colorectal polyps (LNPCPs, ≥20 mm) is as safe and effective as the current standard intensive surveillance. Approximately 760 adults undergoing complete pEMR with margin ablation will be randomized 1:1 into: Standard Surveillance: Colonoscopy at 6, 18, and 48 months Relaxed Surveillance: Colonoscopy at 12 and 48 months All colonoscopies will be performed using high definition white light and narrow band imaging, with biopsies obtained only if recurrence is suspected. The investigators hypothesize that a relaxed surveillance strategy will be non inferior to the current standard intensive surveillance. If non inferiority is demonstrated, the study may support guideline changes toward reduced surveillance frequency after pEMR with margin ablation, potentially decreasing patient burden and healthcare costs.

Background Preterm infants often need respiratory support. HFNV is a non-invasive method with benefits over CPAP, such as reduced nasal trauma and improved feeding. Aim Study the impact of low (2 LPM) vs. high (6 LPM) HFNV flow rates on CO2 levels in preterm infants. Methods Design: Prospective, crossover observational study. Participants: Preterm newborns (24-33.6 weeks' gestation) on HFNV. Procedure: Randomized flow rate adjustments, monitoring tcCO2 and other respiratory parameters over three hours. Outcomes Primary: Change in tcCO2. Secondary: Study terminations due to unsafe CO2 levels and changes in other respiratory metrics. Statistical Analysis Sample size: 45 infants. Analysis: Paired and unpaired t-tests for comparison within and between groups.

Supportive and palliative care play an important role in cancer treatment, and when introduced early can improve quality of life and may even increase median survival rates, as shown in patients with advanced lung cancer. Complementary and integrative medicine (CIM) is a popular supportive approach among oncology patients and is on the rise worldwide. In many countries, homeopathy is being one the CIM methods integrated with a general sense that this treatment is beneficial to the well-being and quality of life (QoL) of cancer patients. In this observational study we will evaluate the feasibility of integrating homeopathic approach in patients attending the complementary and integrative oncology service at the division of oncology in Rambam Health Campus in Haifa, Israel, a major referral comprehensive cancer center. This observational study will evaluate three main ingredients of acceptance: * Obtaining the reasons that patients willing to integrate this supportive approach * Patient acceptance of this supportive approach as well as compliance with the homeopathic approach * Obtaining retrospective subjective information from the patients through validated quality of life questionnaires. (MYCaW, Distress Thermometer, and ESAS-R) Measures which are used routinely in integrative oncology encounters.

Patients with bloodstream infections, hospital acquired pneumonia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB) treated with cefiderocol combined with ampicillin sulbactam will be compared to patients treated treated with colistin alone or colistin combined with meropenem.

Data regarding optimal treatment for extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae blood-stream infection are lacking. Observational studies show conflicting results when comparing treatment with combination beta-lactam-beta-lactamase inhibitor and carbapenems. The investigators aim to evaluate the effect of definitive treatment with meropenem vs. piperacillin-tazobactam on the outcome of patients with bacteremia due to cephalosporin-non-susceptible Enterobacteriaceae. The investigators hypothesize that piperacillin-tazobactam is non-inferior to meropenem.

Fibromyalgia is a chronic condition that causes widespread pain, fatigue, and other symptoms, significantly affecting quality of life. Unfortunately, there are few effective treatments available. Recently, medical cannabis has gained attention as a potential treatment, leading many countries to approve its use for fibromyalgia. However, its success is limited-only about 25% of patients experience meaningful pain relief, and side effects like dizziness or fatigue are common. Not everyone responds to medical cannabis the same way, and researchers think this variability may partly be explained by differences in the gut microbiome-the community of bacteria and other microorganisms living in our digestive system. These microbes are known to influence various aspects of health, including pain and how the body processes medications. Our research focuses on understanding the link between the gut microbiome and fibromyalgia. We propose a study where 150 fibromyalgia patients will be treated with either cannabis oil or a placebo in a double-blind trial. By analyzing their symptoms and gut microbiome, we hope to identify patterns that could predict who will benefit most from cannabis treatment. If successful, this research could lead to more personalized and effective treatment options for fibromyalgia.

This is a randomized placebo-controlled trial in Crohn's disease patients before initiation of anti-tumor necrosis factor-α (anti-TNF) therapy that aims to test the effect of a pre-treatment short course of azithromycin therapy on immunogenicity

Postpartum hemorrhage (PPH) is the leading cause of death related to pregnancy. PPH can lead to blood transfusion, disseminated intravascular coagulation (DIC), hysterectomy, or death. The prophylactic administration of uterotonic agents as part of an active management of the third stage of labor has been proven to reduce rates of PPH. However, even with these treatments, PPH rate is still relatively high, and puts women at risk of heavy bleeding and death. Calcium is a key component in the coagulation cascade and known as factor IV. It has a role in platelet activation, and it is an important co-factor for the activation of factors II and There is a concentration-dependent effect of hypocalcemia on in vitro clot strength in patients at risk of bleeding. Calcium gluconate is the calcium salt of gluconic acid, and it has a relatively strong safety profile. Hypocalcemia is a poor prognostic factor in actively bleeding patients. Calcium has a positive inotropic effect both on skeletal muscle and smooth muscle. The inotropic effect doesn't skip the myometrium, and it is well-established that hypocalcemia can impair myometrial contractility. As so, calcium channel blockers are prescribed as a tocolytic drug and calcium gluconate should be considered as adjuvant therapy for treating PPH duo to atony, in case of prolonged tocolytic or magnesium sulfate use prior to delivery. Studies have already shown an association between low ionized calcium levels and the risk for severe bleeding. In a pilot randomized controlled trial of patients with risk factors for uterine atony, calcium was shown to reduce uterine atony compared to placebo. However, current studies have small sample size and are limited to a high-risk population. There are no recommendations in current guidelines for monitoring calcium levels or prescribing calcium as a prophylactic measure for the third stage of labor, despite atony and coagulopathy being significant causes of PPH. HYPOTHESIS: Administration of Calcium Gluconate at the third stage of elective Cesarean delivery will decrease the rates of blood loss during and after the surgery by reducing the rates of uterine atony and development of coagulopathy, thus has the potential of reducing the incidence of PPH and its complications without severe side effects.

Efgartigimod in Myasthenic Crisis Background Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, characterized by weakness in skeletal muscles. It is associated with the production of autoantibodies, primarily targeting acetylcholine receptors (AchR), and is often complicated by myasthenic crisis, which can lead to severe respiratory failure. Current treatments primarily involve non-specific immunosuppression, which may not provide rapid relief. Aim This study investigates the therapeutic impact of efgartigimod, an FcRn-targeting Fc fragment, on patients experiencing a myasthenic crisis. We hypothesize that efgartigimod is non-inferior to conventional treatments like intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) in terms of clinical efficacy and safety. Study Rationale Efgartigimod aims to reduce pathogenic IgG autoantibodies implicated in MG by accelerating their degradation. This targeted approach could provide faster symptom relief during acute exacerbations compared to existing therapies. Objectives Primary Objective: To assess the non-inferiority of efgartigimod compared to PLEX and IVIG based on MG-ADL improvements. Secondary Objectives: Evaluate safety, tolerability, length of hospital stay, respiratory parameters, need for additional therapies, and one-year outcomes. Primary Endpoint MG-ADL Improvement: Defined as a ≥3-point improvement post-treatment. The comparison will be made using one-month post-treatment assessments, with follow-ups every three months. Secondary Endpoints Safety and tolerability Length of hospital stay Changes in respiratory function Need for rescue therapy in case of clinical deterioration Sample Size The study will recruit 32 patients (16 historical group and 16 interventional group), calculated to detect significant differences in MG-ADL improvements with a significance level of 0.05 and power of 0.80. Patient Recruitment Patients with a confirmed diagnosis of MG who present to the neurology department will be recruited and randomly assigned to either the efgartigimod treatment group or the historical control group receiving standard care (IVIG/PLEX). Inclusion Criteria Adults \> 18 years Confirmed MG diagnosis with generalized weakness (MGFA class II-V) Positive AchR or MuSK antibodies Evidence of myasthenic crisis Informed consent Exclusion Criteria Contraindications to efgartigimod Significant comorbidities affecting study participation Prior exposure to efgartigimod Ongoing infections or conditions exacerbating MG symptoms Recent major surgery or significant renal/hepatic dysfunction Planned Protocol Administer efgartigimod intravenously at 10 mg/kg weekly for four weeks. Total trial duration: 12 months for enrollment and treatment, followed by a 14-month follow-up.

This is a randomized controlled trial investigating whether continuous oxytocin infusion in multiparous women shortens time to delivery, without altering maternal or neonatal outcomes, in augmented deliveries, compared to intermittent infusion.

This is a study proposal for a clinical trial to evaluate the effectiveness of a reduced dose of antenatal betamethasone (a steroid medication) in preventing respiratory problems in late preterm infants (born between 34 and 36 weeks of gestation). The study will be conducted in medical centers in Israel and will involve women who are at high risk for delivering a late preterm infant. The participants will be randomly assigned to receive either a full dose (12 mg) or a quarter dose (3 mg) of betamethasone, administered 24 hours apart. The main outcome measure of the study will be the incidence of respiratory problems or neonatal death within 72 hours of delivery in the two groups. The study is designed to determine if the reduced dose of betamethasone is non-inferior (i.e., not significantly worse) than the full dose in preventing respiratory problems in late preterm infants.

In women with cervical cancer -Squamous cell carcinoma, Adeno carcinoma, Adeno-squamous carcinoma or AIS we want to examine prospectively: 1. Examine if negative HR-HPV after conization to the HR-HPV the women had before conization has a high prognostic value for no residual tumor in the final pathology. 2. To examine if conization in women with cervical tumor up to Stage I B 2 (FIGO 2018) is corelated with better prognosis.

Early oxytocin administration at the 2nd stage of labor is associated with a higher rate of vaginal delivery, shorter second stage duration, and fewer adverse maternal and neonatal outcomes.

A CVA occurs when there is a sudden interruption of blood supply to the brain. Fast identification of CVA is crucial in order to refer the patient to an appropriate medical center as well as to direct him/her to a suitable treatment upon arrival to the Medical Center, in order to minimize the permanent damage to the brain. In this study, we are evaluating a tool for detecting CVA based on EEG (electroencephalograph) data analysis using innovative algorithm. The system is comprised of four electrodes, reference electrode and earphones for auditory stimulation. In the study, 120 patients arriving to the emergency room with decreased consciousness, severe headaches or dizziness will be monitored for five-minute each, with EEG accompanied with auditory stimulation. The EEG analysis will be performed based on the synchronization of the front and back hemispheres. During CVA, specific hemisphere is damaged, therefore desynchronization is expected. The purpose of this study is to develop a tool for identifying CVA in patients who have no clear CVA related signs.

Esophageal cancer continues to be one of the most challenging topics and the subjects of numerous studies. Surgery is the mainstay for curative treatment and the need to improve all aspects of perioperative management in order to reduce morbidity and mortality, continues to be of immense importance. Cited as the sixth most common cause of cancer-related death worldwide, esophageal cancer has a distinct geographic distribution known as the esophageal cancer belt: north central China through the central Asian republics to northern Iran, and from eastern to southern Africa. Squamous-cell carcinoma and adenocarcinoma are the two main histological subtypes of esophageal cancer, in a geographic differentiation as well, with squamous-cell carcinoma as the most common esophageal cancer subtype worldwide. Though adenocarcinoma is at a considerable rise in Western populations and has become the predominant subtype North America, Australia and Europe. Although an ongoing improvement has been marked in the long-term survival after esophagectomy, it is still a highly invasive procedure with serious post-operative complications and entails a high morbidity and mortality rates. Rates of mortality and morbidity range vastly in the literature with 30-day mortality reaching 11-22%. Complication rates up to 50%, with anastomotic leaks as the main complication ranging widely 0-35%. Various risk factors have been proposed as contributors to mortality and morbidity in general and to anastomotic leaks in particular. These include both patient and tumoral characteristics such as premedical history and perioperative factors as tumor location, surgical technique and perioperative treatment. The microbiome as a contributor to a patients' disease progression and management is of great interest in the understanding and better management of cancer patients as a whole and of the gastrointestinal tract in specific. The contribution of the microbiome of a patient to colorectal cancer progression and to anastomotic leaks in the post-operative period has been addressed vastly in the literature in recent years, showing a distinct correlation to specific microbiota profile. Shogan et al. depicted a potential molecular mechanism of bacterial-driven anastomotic leak. It was shown that strains of the commensal organism Enterococcus faecalis could cause anastomotic leakage by causing direct collagen degradation at the site of a freshly constructed anastomosis, and indirectly by bacterial-induced over activation of host matrix metalloproteinase 9 (MMP9). A geographic differentiation in microbiota of Colorectal Cancer (CRC) was also shown by comparing tumor tissue and adjacent tissue of Colorectal Cancer patients from the US and Spain, elaborating yet another aspect of the importance of microbiome of cancer patients. Oropharyngeal microbiome profiling has been proven as a possible predictor for post esophagectomy pneumonia projecting on overall survival as well. A recent study by Rishindra et al from the university of Michigan shows a strong correlation of post esophagectomy anastomotic leaks and increased bacterial variance in preoperative oral and gastric flora. We hypothesize that a correlation exists between microbiome of esophageal cancer patients and post esophagectomy anastomotic leaks. According to former evidence microbiota are integrated into the tumor and therefore the microbial profile of the host (patient) may be represented by tumor microbiota. In this proposed study, we intend to characterize retrospectively the microbial signature of esophageal tumors and to study whether there is a correlation between differential microbial signature and risk of post esophagectomy anastomotic leaks.

The aim of this study is a comparison of induction of labor with a cervical ripening balloon left in place for one hour compared to twelve hours. The primary outcome is time to delivery. Women admitted for induction of labor will be recruited and randomized to either a cervical ripening balloon for one hour or twelve hours. the management of delivery after the extraction of the balloon will be left to the discretion of the attending physician.

Rationale of the study: Gestational diabetes mellitus (GDM) is very common and the rate of women suffering from it expected to increase in the next years. It is associated with maternal and fetal morbidity and the risk is correlated to the patient's degree of glucose control which can be achieved through a change in lifestyle or medication. Several studies have demonstrated the effectiveness of mobile apps in improving obstetric outcomes in GDM. In addition, the LUMEN device is a breathing device that produces dietary and exercise recommendations based on CO2 levels and improves metabolic parameters in patients with type 2 diabetes. No work has been done on its effectiveness in treating GDM. Aims of the study: Comparison of metabolic outcomes in women with gestational diabetes, with or without the use of LUMEN app. Design: This will be an open label parallel group 1:1 randomized-controlled trial Methods: the investigators will recruit women diagnosed with GDM. The women will be randomized to the intervention arm that will use the LUMEN device and app or to the control arm that will use a free mobile tracking app. The women will be required to monitor their blood sugar levels daily and to have GDM follow-up in the feto-maternal outpatient clinic, as is customary in GDM. After the birth, the maternal and neonatal outcome will be recorded. Based on past research data, a recruitment of 170 is needed to demonstrate a 16.7% decrease in insulin use to balance diabetes, with α = 0.05 and β = 80.

The goal of this study is to test whether monitoring insulin levels and using pioglitazone to treat hyperglycemia and hyperinsulinemia in patients treated with Alpelisib for metastatic breast cancer is feasible and safe, and to assess the rates of glycemic control, dose reductions and treatment discontinuation and the progression free survival of patients treated with this regimen.

Exercise capacity is a key factor to evaluate and treat patients in different diseases (e.g. ischemic heart disease, chronic obstructive pulmonary disease, cystic fibrosis). The best way to measure exercise capacity is to perform a cardiopulmonary exercise testing. Normal/reference values in health and disease relate to specific population and subpopulations. The population in Israel is unique in its diversity. Objectives: Data collection of exercise capacity assessment in health and illness in the northern of Israel for future local database. Population: 500 Patients evaluated routinely in the exercise lab (pediatric cardiology institute) and healthy volunteers evaluated as controls. Study design: Prospective observational study. Participants will answer a health related questioner, undergo a physical examination, perform a cardiopulmonary exercise test on a treadmill or a cycle ergometer.