Marienhafe, Germany

Effects of Increasing Mean Arterial Pressure on Renal Function in Patients with Shock and with Elevated Central Venous Pressure

Current recommandation for mean arterial pressure (MAP) target is 65 mmHg for septic shock, but optimal target to prevent acute renal failure (ARF) remains unknown. High central venous pressure (CVP) can lead to acute renal failure through venous congestion , and is associated with acute renal failure in intensive care unit. A decrease of renal perfusion pressure, defined by MAP - CVP, has been shown to be associated with risk of acute renal failure. The main objective of this trial is to evaluate if an optimisation of renal perfusion pressure, by a higher MAP when CVP is high (≥ 12 cmH2O), can improve renal function. In this interventional monocenter trial, each patient will be evaluated during 2 consecutive periods of 6 hours, with a temporary MAP target - Target at 65-70mmHg during 6 hours - Target at 80-85mmHg during 6 hours Patients will be randomized into two groups to define the order of targets. There will be a stratification on previous arterial hypertension. Renal function will be measured at the end of each period.

A Study of DZD9008 Versus Platinum-Based Doublet Chemotherapy in Local Advanced or Metastatic Non-small Cell Lung Cancer (WU-KONG28)

TIKeasy TAblet satisfaCtion (TikTac)

The "Ardoiz" tablet PC will be given to old patients hospitalized in the acute care geriatric unit of the university hospital of Angers. Patients and their relatives will have a free access to "Ardoiz" during their hospitalisation. The maximum duration of use will be 9 days. After the using period, a survey will be proposed to the patients and their relatives. This survey include questions concerning usability (using the validated SUS questionnaire), ergonomics (using non validated specific questionnaire with closed questions oriented on "Ardoiz" device), satisfaction (general and specific questions using non validated questionnaire with forced choice Likert scale in 4 points and closed questions). After recruiting all expected patients and relatives; the survey will also be submitted to the professional caregivers of the unit.

A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations

Enrollment of subjects into Phase 1 will proceed concurrently by age as follows: - Subjects <12 years old will initially be enrolled in the Phase 1 part to determine the pediatric RP2D for this age group; once the pediatric RP2D is determined, subjects age <12 years old may be enrolled into the Phase 2 part of the study. - Subjects 12 to 25 years old will be directly enrolled into the Phase 2 part concurrent with Phase 1 enrollment. Phase 1: Approximately 12 pediatric subjects with locally advanced or metastatic solid tumors, including a primary central nervous system (CNS) tumor, or anaplastic large cell lymphoma (ALCL), with disease progression or who are non-responsive or intolerant to available therapies and for which no standard or available curative therapy exists. Phase 2: Subjects will be enrolled in one of 3 cohorts as follows: Cohort 1: approximately 10-20 subjects with solid tumors characterized by NTRK fusion, TRK tyrosine kinase inhibitor (TKI)-naïve, and centrally confirmed measurable disease at baseline. Cohort 2: approximately 23 subjects with solid tumors characterized by NTRK fusion, TRK TKI-pretreated, and centrally confirmed measurable disease at baseline. Cohort 3: approximately 20 subjects with solid tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease not otherwise eligible for Cohort 1 or 2. As of the current protocol amendment, only patients with ROS1 alterations will be enrolled to this cohort.

Impact of Early Debriefing and Enhanced Educative Components on Direct Oral Anticoagulant Adherence After Venous Thromboembolism.

Venous thromboembolism (VTE) is a frequent multifactorial and potential life-threatening disease. Once VTE has been diagnosed, anticoagulation should be started and prolonged for at least three to six months in order to reduce the risk of fatal and non-fatal recurrences and long-term sequelae. The development of direct oral anticoagulants (DOACs) has represented a major advance in patients' care as there is evidence that DOACs are associated with a decreased risk of bleeding without loss in efficacy and as it simplifies treatment modalities for the patients and the physician. However, as DOACs do not require laboratory monitoring, adherence of anticoagulation is difficult to evaluate and traditional programs built on patients receiving VKA may no longer be applicable to patients on DOAC. In order to increase treatment adherence in patients on DOAC for an acute VTE and to improve the quality of life, the impact of specific educational programs on DOACs, taking in account both therapeutic (DOAC) and medical illness (VTE) dimensions needs to be investigated. Design The "DEBRIEF-VTE" trial is a multicenter randomized trial with blind evaluation and using a Zelen randomization process comparing a standardized follow-up visit at one month associated with a "debriefing and enhanced educative components" versus a standardized follow-up visit at one month alone (i.e.; without debriefing process). All patients meeting the inclusion and none of the exclusion criteria are eligible for randomization. They will be randomized 1:1 to one of two allocated groups: - Experimental group: a standardized follow-up visit at one month associated with "debriefing and enhanced educative component" - Control group: a standardized follow-up visit at one month alone (i.e.; without "debriefing and educative component") Randomization will be performed using a two-step methodology described by Zelen et al. - Stratification by: - Center - DVT or PE - Presence of a major risk factor (either transient or persistent) or not (unprovoked VTE) At visit 1 (inclusion, 0-7 days): Inclusion of patients using the first written informed consent to accept a standard follow-up (visit at 1 month and 6 months) without mentioning randomization at one month performed in order to allocate patients to have, or to not have, debriefing and enhanced educative components. Study medication will be administered with complete explanation about doses and a classical therapeutic information regarding DOAC and clinical signs of recurrent VTE and bleeding (one treatment box with 400 pills of apixaban at 5 mg for the first 6 months of therapy) will be performed. Visit 2 (30 days): - Before the visit 2, review of all the inclusion and exclusion criteria and compute creatinine clearance using Cockcroft-Gault method ; if all eligibility criteria are satisfied, randomization of the patient; - After randomization, during the visit 2: - For patients allocated to the experimental group: signature of the second written informed consent describing the debriefing and enhanced educative components and objective on quality of life - For patients allocated to the control group: no second written informed consent is required Visit 3/ET (180 days): - Evaluate quality of life (PembQOL if PE, VEINES-Qol if DVT, EQ-5D for all patients), residual symptoms (mMRC and MDP scale if PE, Villalta if DVT) depression (HAD), recurrent VTE, bleeding, hospitalizations, death The primary objective is to demonstrate that, in patients with an acute episode of VTE treated for at least 6 months, early debriefing and enhanced educative components added to a standardized visit one month after an acute VTE is associated with an increased adherence to apixaban therapy at 6 months than after a standardized visit alone at one month (adherence measured by the MEMSCap™ Medication Event Monitoring System Cap (WestRock, USA & Switzerland). In patients with an acute episode of VTE treated for at least 6 months, the main hypothesis is that early debriefing and educative components added to a standardized visit one month after an acute VTE has the potential to improve patient's adherence to APIXABAN therapy at 6 months of follow-up. Secondary objectives are to evaluate the impact of early debriefing and enhanced educative components added to a standardized visit one month after an acute VTE on the following at 6 months of treatment : quality of life (EQ-5D for all, PembQOL if PE, VEINES-Qol if DVT), residual symptoms (MMRC and multidimensional dyspnea profile(MDP) scales if PE, Villalta if DVT), depression (HAD), recurrent VTE, bleeding,hospitalizations and death. 150 patients will be included Duration of the inclusion period: 18 months Duration of participation for each patient: 6 months Total duration of the study: 24 months

AntiCoagulants and COGnition

Detailed Description: Vitamin K antagonists (VKAs) are commonly used for their role in hemostasis by interfering with vitamin K cycle decreasing the bioavailability of the vitamin K active form. In addition to a role in blood coagulation, vitamin K participates in brain health and function by regulating the synthesis of sphingolipids, a constituent of the myelins sheath and the neurons membrane, and through the biological activation of vitamin K-dependent proteins (VKDPs) involved in neuron survival. Epidemiological studies have reported a positive association between higher serum vitamin K concentration and better verbal episodic memory performance in older adults, and an inverse association between dietary vitamin K intakes and behavioural disorders and cognitive complaint. The clinical implication is that the use of VKAs, which deplete the active form of vitamin K, may be responsible for Central Nervous System (CNS) disorders. CNS abnormalities were observed in newborns exposed in utero to VKA. Similarly, the investigators and other researchers reported that the use of VKAs (especially fluindione) was directly associated with cognitive decline (notably executive dysfunction) and hippocampal atrophy in older adults, even while taking into account the history of atrial fibrillation, stroke and vascular brain changes. These cross-sectional and longitudinal studies were yet limited by their observational design. Clinical trials are now warranted to explore the effect on cognition of VKAs against direct oral anticoagulants (DOACs), whose indications are similar but whose mechanism does not interfere with vitamin K. The favorable impact of the use of DOACs compared to VKA in the incidence of dementia was also observed in a US retrospective population-based study of patients managed per routine clinical care. The investigators hypothesize that VKAs have a deleterious impact on cognition and brain morphology compared to DOACs, due to the decrease in vitamin K bioavailability. A review of the published clinical trials comparing the effects of VKAs and DOACs, especially rivaroxaban, shows that cognition and brain volume were not assessed as outcomes in these trials.

Brain-injured Patients Extubation Readiness Study

Severe brain-injured patients need mechanical ventilation with tracheal intubation. After treatment of the acute neurological condition, weaning of the mechanical ventilation has to be initiated notably to prevent ventilator associated pneumonia and others complications. Nevertheless, extubation failure is very common in this population due to residual neurological impairment with airway control alteration. Guidelines about weaning of mechanical ventilation and extubation exclude brain-injured patients with a residual impaired consciousness. In 2017, a simple and pragmatic extubation readiness clinical score was validated in a prospective observational cohort study of 140 brain injured patients. (Godet et al. Anesthesiology. 2017 Jan;126(1):104-114) In this study, brain injured patients with residual impaired consciousness who succeeded a spontaneous breathing trial were extubated. In multivariate analysis, 4 clinical elements were associated with extubation success. A prediction score was determined using the odds ratio such as followed : 1. Deglutition: 3 points if present 2. Gag reflex: 4 points if present 3. Cough: 4 points if present 4. CRS-R Score, visual item > 2, 3 points if present, 1 point if not For a cut-off value of 9, extubation failure could be predicted with a sensibility of 84%, a specificity of 75%, a positive predictive value of 89% and a negative predictive value of 66%. In order to participate, brain-injured patients will have to succeed a spontaneous breathing trial and meet all inclusion criteria, including not being able to obey to simple orders without sedation. Using a stepped wedge randomisation process with intensive care units as clusters, patients will be weaned and extubated under usual care or using the extubation readiness clinical score. The authors' hypothesis is that this clinical score will allow physicians to extubate patients at the right time interval and prevent extubation failure in this frail population.

Study of Genetic Determinants in Alcoholic Hepatitis and Establishment of a Multicenter Prospective Cohort of Patients With Alcoholic Liver Disease

A 3 Years Naturalistic Cohort Survey Of Virtue® Male Sling System For Male Stress Urinary Incontinence

This project will be launched after the first introduction of Virtue® Male Sling in Europe. This study is a multicenter prospective, non-interventional (i.e. naturalistic) post-marketing clinical follow up of men with urinary incontinence implanted with Virtue® Male Sling System by urologists who are experienced in the device. The patient will be followed for 12 months in routine real world clinical practice except for administration of subject questionnaire(s). Routine visits will be performed approximately at baseline (preoperative and implantation period), between 1 and 3 months (immediate post-operative period) and 12 months. Then questionnaires will be mailed annually during 2 additional years.

Home Airway Clearance in CF Patients