cyrilzakka/clinical-trials huggingface dataset:
Decitabine in Patients With Chronic Myelomonocytic Leukemia (CMML)

The aim of this study is to determine the therapeutic efficacy of Decitabine in patients with chronic myelomonocytic leukemia (CMML) diagnosis according to WHO criteria either untreated or previously treated with Hydrea or Etoposide (given orally), non intensive chemotherapy or intensive chemotherapy given more than 3 months before inclusion.


Eligibility Criteria:
Inclusion Criteria:

* Age 18 or older
* CMML diagnosis according to WHO criteria
* Stable excess in blood monocytes,\>1x10G/l and \>10% of WBC
* Bone marrow blasts \<20%
* Dysplasia of at least one lineage or clonality marker or blood monocytosis during more than 3 months w/o other explanation
* With:

  * if WBC \< or= 12 000/mm3: IPSS high or intermediate 2
  * if WBC \> 12 000/mm3: at least two of the following criteria: blast cells \> 5% in the bone marrow, clonal cytogenetic abnormality other than t(5;12)(q33;p13), anemia (Hb \< 100 g/l), thrombocytopenia (platelet count \< 100G/l), splenomegaly \> 5 cm below costal margin, extramedullary localization
* Either untreated or previously treated with
* Hydrea or Etoposide given orally
* non intensive chemotherapy
* intensive chemotherapy given more than 3 months before inclusion
* With performance status 0-2 on the ECOG scale
* With estimated life expectancy of at least 12 weeks
* With adequate organ function including the following:

  * Hepatic: total bilirubin \< 1.5 times upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) \< 3 times ULN
  * Renal: serum creatinine \< 1.5 times ULN, creatinine clearance \> 30 ml/min
* With informed consent
* Negative pregnancy and adequate contraception if relevant

Exclusion Criteria:

* Myeloproliferative/myelodysplastic syndrome other than CMML
* Acute blastic transformation of CMML with bone marrow blasts\>20%
* Patients eligible for allogenic bone marrow transplantation with identified donor
* CMML with t(5;12) or PDGFbetaR rearrangement that could receive Imatinib
* Previous treatment with a hypomethylating agent
* Age \< 18 years old
* Pregnancy or breastfeeding
* Performance status\> 2 on the ECOG Scale
* Estimated life expectancy \< 12 weeks
* Serious concomitant systemic disorder, including active bacterial, fungal or viral infection, that in the opinion of the investigator would compromise the safety of the patient and/or his/her ability to complete the study
A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012)

This study is designed to evaluate the efficacy of three dose regimens of gefapixant (\[MK-7264\] 7.5 mg, 20 mg, and 50 mg) relative to placebo in reducing awake objective cough frequency. The primary hypothesis for this trial is that at least one dose regimen of gefapixant is superior to placebo with respect to the mean change from baseline in awake cough frequency (on the log scale).


Eligibility Criteria:
Inclusion Criteria:

* Women and Men between 18 and 80 years of age inclusive
* Have refractory chronic cough
* Women of child-bearing potential must use 2 forms of acceptable birth control - Have provided written informed consent.
* Are willing and able to comply with all aspects of the protocol

Exclusion Criteria:

* Current smoker
* Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio \<60%
* History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit
* History of opioid use within 1 week of the Baseline Visit
* Body mass index (BMI) \<18 kg/m\^2 or ≥ 40 kg/m\^2
* History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with \<3 excised basal cell carcinomas)
* Screening systolic blood pressure (SBP) \>160 mm Hg or a diastolic blood pressure (DBP) \>90 mm Hg
* Clinically significant abnormal electrocardiogram (ECG) at Screening
* Significantly abnormal laboratory tests at Screening
* Pregnant or Breastfeeding
* Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the participant inappropriate for entry into this trial
Assessment of the Safety and Effectiveness of Cortical Stimulation in Subjects With Major Depressive Disorder

The purpose of this study is to assess the safety and effectiveness of cortical stimulation to the cerebral cortex of subjects who have suffered from treatment-resistant depression and have failed routine attempts at controlling their depression.

Major depressive disorders are the most common of all psychiatric disorders. The World Health Organization estimates that 340 million people worldwide suffer from an episode of major depression each year, accounting for 4.4% of the overall global disease burden. In the United States, about 9.5% or 19 million people are affected by a depressive disorder, with a lifetime risk of about 17% for a major depressive disorder.

While depression can be effectively treated in the majority of patients by medication and psychotherapy, up to 20% of patients fail to respond. Electroconvulsive Therapy (ECT) is effective in approximately 70% of cases where antidepressant medications do not provide sufficient relief of symptoms. However, as many as 20-50% of the people who respond well to a course of ECT relapse within 6 months, therefore, periodic maintenance therapy is often required.

For those patients who are resistant to the therapies noted above, more invasive approaches have been used, including Vagus Nerve Stimulation (VNS) and more recently Deep Brain Stimulation (DBS).

Direct cortical stimulation of the cortex via an implanted device system may provide long lasting benefit with minimal side effects. The current study seeks to assess in a feasibility study the safety and efficacy of stimulating the prefrontal cortex in patients with major depressive disorder.

Eligibility Criteria:
Inclusion Criteria:

* Current major depressive episode (MDE) lasting for at least two years, or at least 4 lifetime MDEs with the current episode lasting for at least one year
* Severe depression at study entry defined as a minimum score of 20 on the Hamilton Depression Rating Scale
* Failed response to at least four different antidepressant treatments

Exclusion Criteria:

* Axis I psychiatric diagnoses including schizophrenia, bipolar disorder, panic disorder, obsessive compulsive disorder, or evidence of global cognitive impairment
* An Axis II diagnoses of either: a) borderline personality disorder, or b) histrionic personality disorder
* Electroconvulsive therapy within 6 months prior to enrollment
* Known need of electroconvulsive therapy while the investigational device is implanted
* History of seizure disorder or status epilepticus
Assessment of Obstetric, Fetal and Neonatal Risks and Vertical SARS-CoV-2 Transmission During COVID-19 Pandemic

A new coronavirus (COVID-19) highlighted at the end of 2019 in China is spreading across all continents. Most often at the origin of a mild infectious syndrome, associating benign symptoms (such as fever, cough, and headache) to different degrees, COVID-19 can cause serious pulmonary pathologies and sometimes death. Data on the consequences during pregnancy are limited. The first Chinese data published seem to show that the symptoms in pregnant women are the same as those of the general population. There are no cases of intrauterine maternal-fetal transmission, but cases of newborns infected early suggest that there could be vertical intrauterine, perpartum or neonatal transmission. Prematurity and cases of respiratory distress in newborns of infected mothers have been described. Subsequently, an in-depth analysis of cases in pregnant women and pregnancy issues are necessary in order to improve knowledge on the subject.

The main objective of this project is to set up a biological and tissue collection in order to study the transplacental passage of the SARS-CoV-2 virus, and the pregnancy outcomes (miscarriage, intra uterine fetal death, medical termination of pregnancy or living birth) during COVID-19 pandemic. The biological and tissue collection will be made up of systematic samples taken from parturient women and their pregnancy outcome at the time of their arrival at the maternity unit to deliver whatever their term and pregnancy outcome. This inclusion will concern all pregnant women, both symptomatic and asymptomatic positive COVID-19 women, and negative COVID-19 women. All women included will have a serological test to check their immunity status to SARS-CoV-2 in order to study pregnant women with an unnoticed COVID-19 infection during their pregnancy. The inclusion time will extend from the epidemic period until a year after, in order to document the outcomes of pregnant women potentially exposed to SARS-CoV-2 in early pregnancy. Samples analyses will be carried out after the epidemic peak to not overload laboratories in times of crisis.

The challenge is to have a better knowledge of the SARS-CoV-2 epidemiological and virological characteristics in particular its involvement in maternal-fetal morbidity and mortality, and to better understand the organs affected and the pathways of contamination within this particular mother-child duo.

Eligibility Criteria:
Inclusion Criteria:

* Women over 18 years old on the date of inclusion
* Pregnant women coming to deliver in the Paule de Viguier maternity unit of Toulouse's University Hospital between April 2020 and April 2021 regardless the pregnancy outcomes (live births, IUFD, miscarriages, medical termination of pregnancy ) and the term
* Women affiliated to a social security system (including AME)

Exclusion Criteria:

* Voluntary termination of pregnancy
* Language barrier
* Patient under a legal protection measure (guardianship, curatorship, or safeguard of justice)
Desensitization in Kidney Allograft Using Daratumumab

Patients highly allosensitized against HLA antigen awaiting for a kidney transplant have less compatible transplants to them, increasing their waitlist time and mortality. Current desensitization strategies need to be improved with a high remaining acute rejection rate in this population and a substantial survival benefit which is not uniformly reported in the literature. The investigators propose to use daratumumab, a human IgG1 (Immunoglobulin Gamma-1) monoclonal antibody directed against the CD38 molecule (cluster of differentiation 38) witch induce response in refractory multiple myeloma by depleting plasma cells, as a new agent of desensitization. The study will address the hypothesis that daratumumab can lead to a significant decrease in calculated panel reactive antibodies by elimination of anti-HLA antibodies-producing plasma cells and facilitate the access to transplantation with a safety profile in highly sensitized patients registered in our kidney transplantation center.


Eligibility Criteria:
Inclusion Criteria:

* Adults ≥ 18 years awaiting a kidney allograft transplantation
* Registration on the French National kidney allograft waiting-list for at least three years
* cPRA ≥ 95% for at least three years
* COVID-19 vaccination using Pfizer BioNtech vaccine for: Patients who have never been infected with COVID-19, inclusion at least one month after the third dose OR Patients previously infected with COVID-19 proved with PCR or serology, inclusion at least one month after the second injection of Pfizer BioNtech vaccine.
* Effective contraception up to three months after the end of treatment
* Informed consent obtained in accordance with local regulations;
* Affiliation to a social security regime.

Exclusion Criteria:

* Refusal of COVID-19 vaccination using Pfizer BioNtech vaccine
* Hypersensitivity to daratumumab or to any of the excipients),
* Known allergy to methylprednisolone and its excipients or to diphenhydramine and its excipients or to acetaminophen and its excipients or to valacyclovir and its excipients.
* Severe hepatocellular insufficiency
* Psychotic state not yet controlled by treatment
* Patient refusal
* Pregnant or breastfeeding woman or ineffective contraception
* Active neoplasia
* Active infection
* Active HBV infection, including HBsAg positive at screening
* Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants
* Persons deprived of their liberty by judicial or administrative decision,
* Persons under legal protection/safeguard of justice,
* Patients under duress psychiatric care,
* Persons admitted to a health or social institution
* Patient on AME (state medical aid)
* Contraindication to kidney transplantation
A Phase 1, Drug Interaction Study Between AVP-786 and Paroxetine and Between AVP-786 and Duloxetine in Healthy Subjects

To assess steady state pharmacokinetics (PK), safety and tolerability between AVP-786 (deuterated \[d6\] dextromethorphan hydrobromide \[DM\]/quinidine sulfate \[Q\]) and paroxetine and between AVP-786 and duloxetine.


Eligibility Criteria:
Inclusion Criteria:

* Healthy adult males and females
* 18 - 50 years of age
* BMI 18 - 30 kg/m2

Exclusion Criteria:

* History or presence of significant disease
* History of substance abuse and/or alcohol abuse with the past 3 years
* Use of tobacco-containing or nicotine-containing products within 6 months
* Use of any prescription or the over-the-counter medications within 14 days
Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma

The management of patients with uterine leiomyosarcomas poses many difficulties. Despite 60% of women present with disease limited to the uterus, cure rates range from 20 to 60%. Patients with metastatic disease at diagnosis or who recur after initial treatment have a dismal prognosis and, except for a subset of selected patients with completely resectable disease, the median survival is less than one year. Treatment options for recurrent/metastatic uterine leiomyosarcoma are limited. The most active drugs are doxorubicin ± ifosfamide and gemcitabine + docetaxel (GD) with response rate of 25-55% and 27-53%, respectively. Both these regimens have been increasingly used in the last years also in the adjuvant setting. For relapsed patients other drugs have been tested as single agent but negligible activity was observed.

Trabectedin (Yondelis® -T) is a marine-derived cytotoxic approved by EMEA. It is indicated for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide or who are unsuitable to receive these agents. Among STS, activity has been mainly detected in synovial sarcoma, liposarcoma and leiomyosarcoma. Although the response rate did not exceed 10%, T was demonstrated to provide disease control, with progression arrest rates exceeding 50% and progression-free survival rates exceeding 20% at 6 months. So far no phase II studies tested the activity of T in uterine leiomyosarcoma specifically. This study is aimed at evaluating the activity of T (arm A) in advanced uterine leiomyosarcomas, having GD (arm B) as an internal control In parallel translational studies will be performed to identify factors predictive of the activity of T in this specific histotype.


Eligibility Criteria:
Inclusion Criteria:

1. Histologically proven uterine leiomyosarcoma.
2. Persistent or locally relapsed and/or metastatic disease.
3. At least one previous systemic treatment with an anthracycline ± ifosfamide or gemcitabine ± docetaxel.
4. Measurable disease, as defined by RECIST criteria.
5. ECOG PS \<=2.
6. Age \>= 18 years.
7. A minimum of 3 weeks since prior tumor directed therapy
8. Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower.
9. Adequate haematological function.
10. Adequate renal function.
11. Adequate liver function.
12. Signed informed consent.

Exclusion Criteria:

1. Prior exposure to Trabectedin.
2. Peripheral neuropathy, Grade 2 or higher.
3. History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse.
4. Known CNS metastases.
5. Active viral hepatitis or chronic liver disease.
6. Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias.
7. Active major infection.
8. Other serious concomitant illnesses
Ropinirole in the Treatment of Bipolar Depression

To demonstrate efficacy and safety of Requip in in treating bipolar depression.

This study is 8 weeks long, with an optional additional 8 weeks. The study is placebo-controlled and patients are randomized to receive either ropinerol or placebo. Changes in depression, anxiety and overall psychiatric symptoms will be monitored during participation.

Eligibility Criteria:
Inclusion Criteria:

* Meet DSM-IV criteria for bipolar disorder
* Current MADRS score \> 16
* Current MRS-SADS score \< 10
* Prior to participation in this study, each subject must sign an informed consent.
* All patients will be required to also take at least one other mood-stabilizing agent, defined as a standard agent (lithium, valproate, carbamazepine) or a novel anticonvulsant agent (oxcarbazepine, gabapentin, topiramate). If patients are not taking any of these agents on study initiation, they will be required to start one of these agents at study initiation. Study inclusion criteria must be met after at least 2 weeks of treatment with one of these mood-stabilizing agents.

Exclusion Criteria:

* Any serious acute medical illness
* Any clinically serious evidence of suicidality or score of 3 or greater on suicide item on MADRS scale
Stratification of the Acute Respiratory Distress Syndrome

The American-European Consensus Conference (AECC) and the Berlin definitions of the Acute Respiratory Distress Syndrome (ARDS) could be adequate for epidemiologic studies, but it is not adequate for inclusion of patients into therapeutic clinical trials. Despite recent reports on the effects of standardized ventilator settings on PaO2/FIO2 and fulfillment of AECC and Berlin definitions of ARDS, it is still a matter of debate whether the assessment of hypoxemia at 24 hours is the most appropriate tool for stratifying lung severity in patients with ARDS. The investigators will perform an observational, multicenter, prospective audit in a network of intensive care units in Spain and China for validating and confirming that the assessment of hypoxemia at 24 hours after ARDS onset is the most valuable tool for stratifying and predicting outcome in patients with ARDS.

In 1994, the American-European Consensus Conference (AECC) defined ARDS as follows: 1) acute and sudden onset of severe respiratory distress, 2) bilateral infiltrates on frontal chest radiograph, 3) absence of left atrial hypertension or no clinical signs of left heart failure, and 4) severe hypoxemia, as PaO2/FiO2 ratio \<200 mmHg, regardless of FIO2 or PEEP levels. Although this definition could be adequate for epidemiologic studies, it is not adequate for inclusion of patients into therapeutic clinical trials. In 2012, a proposal for updating the ARDS definition (the Berlin criteria) was published and an empirical classification was proposed according to three PaO2/FiO2 cut-off values at ARDS onset: severe (≤100 mmHg), moderate (\>100-≤200), and mild (\>200-≤300) on PEEP≥5 cmH2O. However, despite that there is sufficient evidence about the interactions between PEEP and FiO2, the Berlin criteria did not mandate the assessment of hypoxemia at 24 hours under standarized guidelines.

The PaO2/FIO2 can be easily manipulated. Alterations in PEEP and FIO2 can dramatically change the PaO2/FIO2. Despite recent reports on the effects of standardized ventilator settings on PaO2/FIO2 and fulfillment of AECC definitions of ARDS, it is still a matter of debate whether the assessment of hypoxemia at 24 hours is the most appropriate tool for stratifying lung severity in patients with ARDS.

The investigators will examine whether the assessment of hypoxemia at 24 h after ARDS diagnosis under standard guidelines for ventilatory management have an impact on the stratification of lung severity and on predicting mortality of ARDS patients in the intensive care unit.

Eligibility Criteria:
Inclusion Criteria:

* Patients meeting the AECC definition for ARDS on PEEP greater or equal than 5 cmH2O (or the Berlin criteria for moderate and severe ARDS).

Exclusion Criteria:

* None
Safety Study of Univers® Revers Shoulder Prosthesis

The primary safety objective is to demonstrate that severe device-related complication (Serious Adverse Device Effect = SADE) occur within 2 years after prosthesis implantation at a rate of less than 2%. Such adverse events include (but are not limited to) revisions due to dislocation or glenoid loosening, septic arthritis and scapular fractures requiring surgical repair.

Reverse shoulder arthroplasty and its principles are still recognized today as the gold standard for treatment of degenerative arthropathy of the shoulder associated with an irreparable tear of the rotator cuff. The new Arthrex Univers® Revers Shoulder Prosthesis shows a large and narrow range of components, whether it is a stem, cup, spacer, inlay or glenosphere. Adjustment can be done in very small steps to match anatomic and biomechanic needs. The Arthrex Univers Revers Shoulder Prosthesis is the only device up to date that can be configured in two different inclination angles without any limitation in component use.

This multicentre case-series has the goal to evaluate whether patients with rotator cuff tear arthropathy benefit from the Univers® Revers shoulder prosthesis in terms of low complication risk, as well as high function and quality of life.

Eligibility Criteria:
Inclusion Criteria:

* Patient aged 18 years and over
* Patient with primary omarthrosis or secondary osteoarthritis associated with insufficiency in the centering function of the rotator cuff

and

• Willing and able to give written informed consent to participate in the study including all follow-up examinations

Exclusion Criteria:

* Previous ipsilateral shoulder arthroplasty
* Acute shoulder trauma
* Post-traumatic secondary osteoarthritis
* Rheumatoid arthritis
* General medical contraindication to surgery
* Known hypersensitivity to the materials used
* Tumour / malignoma
* Any disease process that would preclude accurate evaluation (e.g. neuromuscular, psychiatric or metabolic disorder)
* Bacterial infection at the time point of operation
* Recent history of substance abuse
* Legal incompetence
* Pregnancy or
* Participation in any other medical device or medicinal product study within the previous months that could influence the results of the present study