cyrilzakka/clinical-trials huggingface dataset:
Phase I Trial of Afatinib and Trastuzumab in HER2 Overexpressing Cancer.

The aim of the study is to determine the Maximum Tolerated Dose (MTD) of afatinib in combination with 3-weekly trastuzumab in HER2 overexpressing cancer and to assess the efficacy of afatinib given at the MTD dosage, with 3-weekly trastuzumab in HER2 overexpressing metastatic breast cancer.


Eligibility Criteria:
Inclusion criteria:

1. Patients aged 18 years and older
2. Patients with cancers overexpressing HER2 by Immunohistochemistry test( IHC) 3+ and/or IHC 2+ with positive gene amplification by FISH (confirmation on archived tissue needed)
3. Written informed consent that is consistent with ICH-GCP guidelines.
4. Patients must be eligible for treatment with trastuzumab.
5. Patients must have adequate organ function (kidney, liver, bone marrow, cardiac)
6. Eastern Cooperative Oncology Group (ECOG) = 0 or 1.
7. Measurable disease according to RECIST 1.1 (Phase Ib).

Exclusion criteria:

1. Active brain metastases.
2. Prior treatment with erbB family targeting therapies within the past four weeks before start of therapy or concomitantly with the trial other than trastuzumab and/or lapatinib.
3. Patients having more than 2 lines of chemotherapy for the treatment of metastatic breast cancer (Phase Ib).
Discontinuing Inappropriate Medication in Nursing Home Residents

Nursing home residents are among the frailest patient groups with a high number of co-morbidities and a high use of medicines. Inappropriate polypharmacy (i.e. often overprescribing) is one of the major problems in the nursing home population increasing the number of adverse drug reactions, falls, hospital admissions, mortality as well as having an impact on health care utilization. Multidisciplinary medication reviews have a great potential to reduce inappropriate medication use. The purpose of this study is to determine the efficacy of a multidisciplinary medication review model focussing on discontinuing inappropriate medication in a cluster randomized controlled trial in 600 nursing home residents. The primary outcome measure is the difference in proportion of residents who successfully discontinued medication between intervention and control group after four months. Secondary outcome measures will be the drug burden index, adverse drug withdrawal events related to the discontinued medication, death, referral to hospitals and quality of life.


Eligibility Criteria:
Nursing Home Wards:

Inclusion criteria:

* Long stay ward
* Capability and commitment to perform a multidisciplinary multistep medication review.

Exclusion criteria:

* Short stay, revalidation or observation wards
* Specialized ward where patients with an atypical etiology are cared for.
* Elderly care physicians who have recently received or who are to receive recertification at short notice with regard to systematic medication review methodology.
* Participation in other studies aimed at improving the quality of drug prescription (in the past 12 months).

Nursing Home Residents:

Inclusion criteria:

* A life expectancy of \>4 weeks as judged by the treating elderly care physician.
* IC provided by patients themselves or provided by a legal representative for incapacitated patients.

Exclusion criteria:

* Refusal of treatment with medicines.
* Having received a multidisciplinary systematic medication review in the past 6 months.
* Being terminally ill and having a life expectancy ≤ 4 weeks as judged by the treating elderly care physician.
* Other reasons at the discretion of the elderly care physician / nursing staff
Safety and Efficacy of EPI-743 in Patients With Friedreich's Ataxia

The purpose of this study is to examine the effects of EPI-743 on visual function and neurologic function in patients with Friedreich's ataxia.


Eligibility Criteria:
Inclusion Criteria:

1. Diagnosis of genetically confirmed Friedreich's ataxia
2. Visual acuity at baseline more than 15 letters on EDTRS at four meters
3. FARS score of 20 to 90
4. Agreement to use contraception if within reproductive years (see specifics in section D1, page 21)
5. Hormone replacement therapy, if used, must remain stable for the duration of the study
6. Willingness and ability to comply with study procedures
7. Willingness and ability to arrive at study site day prior to evaluations
8. Abstention from use of dietary supplements and non-prescribed medications at least 30 days prior to initiation of treatment and for the duration of the study. This would specifically include idebenone, Coenzyme Q10 and vitamin E
9. Abstention from use of other investigative or non-approved drugs within 30 days of enrollment and for the duration of the study

Exclusion Criteria:

1. Allergy to EPI-743 or sesame oil or nuts
2. Clinically significant bleeding condition or abnormal PT/PTT INR (INR \> two; PTT \> two-times normal)
3. Liver insufficiency with LFTs greater than three-times upper normal limit at screening
4. Renal insufficiency with creatinine \> 1.5 at screening
5. Fat malabsorption syndromes
6. Any other respiratory chain diseases of the mitochondria or inborn errors of metabolism
7. Any other ophthalmologic conditions
8. History of alcohol or drug abuse
9. Clinically significant cardiomyopathy with ejection fraction \< 40 percent at screening
10. Clinically significant arrhythmia within past two years requiring treatment
11. Anticoagulant therapy within 30 days of enrollment.
Study to Evaluate Pharmacokinetics, Pharmacodynamics, and Safety of Sargramostim Administered Subcutaneously, Intravenously, or by Inhalation

This single center, single ascending dose (SAD) and repeat dose study in healthy adults comprises 2 parts. Part 1 will consist of 6 SAD cohorts, in which different dose levels of sargramostim will be given by intravenous (IV) infusion, subcutaneous (SC) injection, or inhalation (IH) administration. Part 2 will consist of 1 repeat dose cohort in which sargramostim will begiven by SC administration.

Blood samples for PK assessment will be collected before and over 24 hours after each study drug administration. Blood samples for PD assessment will be collected before and up to 14 days after drug administration in Part 1, as well as before the first and up to 14 days after the second drug administration in Part 2. Safety and tolerability will be assessed throughout the study. For Cohort 5 of Part 1 only, 3 subjects will provide a CSF sample for PK assessmen tonce after SC drug administration.


Eligibility Criteria:
Inclusion Criteria:

* Healthy adult male and female participants
* Nonsmoker or ex-smoker
* Able to provide informed consent and comply with all study procedures
* Body Mass Index within 18.5-30.0 kilograms/meter squared, inclusive
* Females of childbearing potential willing to use highly-effective method of birth control.

Exclusion Criteria:

* Females who are pregnant or breastfeeding
* History of allergic to sargramostim or its excipients, other human GM-CSFs, or other yeast-derived products.
* History of severe allergic reactions to other drugs.
* History of or any current medical condition or laboratory finding that may jeopardize completion of the study, present an increased risk to the subject, or compromise interpretation of the study. .
* Immunization with COVID-19 vaccine within 14 days of the study.
* Scheduled immunization with COVID-19 vaccine during the study
* Use of prescription drugs within 28 days of the study or requirement for maintenance drugs during the study.
* Participation in another investigational drug study within 28 days
Evaluation of Breast CT

The investigators have studied the potential of breast computed tomography (bCT) for breast imaging under an NIH-funded Biomedical Research Partnership (BRP) grant (R01 EB002138-10), and 4 breast CT scanners have been developed that have imaged over 600 women to date (under more than one IRB-approved protocol). The BRP grant cannot be renewed, and with this (resubmitted) R01 grant application, the investigators seek to finalize the investigators' research in breast CT - The specific aims have been significantly modified as a result of the first critique, and the investigators now focus on a narrower set of remaining issues.

This version of the protocol will add breast magnetic resonance imaging (MRI) to the experimental procedures.

Clinical evaluation: Four hundred women who will be having breast biopsy as part of their standard care (BIRADS 4 and 5) will be recruited to undergo additional imaging prior to biopsy, including (research) pre-and post-contrast enhanced breast CT imaging of both breasts, as well as (standard, FDA approved) contrast enhanced breast MRI. The potential of non-contrast enhanced breast CT will be compared using receiver operating characteristic (ROC) methodology against mammography alone, as well as with mammography + tomosynthesis. The breast CT images (including both pre-and post-contrast images) will be compared using ROC methodology against standard-of-care contrast-enhanced MRI (which includes both non-contrast and contrast images). The results of the clinical trials proposed in this investigation should provide strong evidence in regards to the potential of breast CT for breast cancer screening in the normal risk and high risk populations.

Eligibility Criteria:
Inclusion Criteria:

* Age at least 35 years old
* Diagnostic findings from prior mammography highly suggestive of breast malignancy (BI- RADS® category 4 or BI-RADS® category 5)
* Not pregnant or breast-feeding
* Ability to lie motionless for up to 5 minutes

Exclusion Criteria:

* Recent breast biopsy
* History of moderate or severe reaction to contrast agent injection
* History of Allergy to Iodine
* History of multiple food and/or drug allergy
* Currently taking Glucophage or Glucovance (Metformin)
* History of Chronic Asthma
* History of Diabetes Mellitus
* Renal (kidney) disease, or solitary kidney
* Recent lab tests showing elevated serum creatinine (≥ 1.5 mg/dL)
* Recent lab tests showing estimated glomerular filtration rate (eGFR) ≤ 60 ml/minute
* Positive urine pregnancy test or currently breast-feeding
* Inability to understand the risks and benefits of the study
* The standard MRI contraindications apply, including but not limited to: having a pacemaker or other implanted electronic device, metal foreign bodies within the eye, aneurysm clips, heart valve prosthesis, vascular stents, coils, intrauterine devices (IUDs), inferior vena cava (IVC) filters, gunshot wounds with retained bullet fragments.
Methylene Blue in Severe Sepsis and Septic Shock

This study is to see whether the intravenous administration of methylene blue improves the outcome in severe sepsis and septic shock.

The mortality of septic shock is still high ranging from 30 to 50%. Vasopressor is the main part in managing septic shock, but the choice of vasopressor is still under-investigated, and area of uncertainty.

The response to vasopressor is sometimes unsatisfactory, and in that case, the outcome of the patients is poor.

Recently, small size clinical trial has investigated the effect of methylene blue (MB), and showed promising results. However, large sized phase III trial has not been performed yet.

Large sized phase III clinical trial is needed to establish the effect of MB in septic shock.

Eligibility Criteria:
Inclusion Criteria:

* Septic shock meeting the criteria of 2012 surviving sepsis campaign
* Need the norepinephrine of over 0.2microgram/kg/min

Exclusion Criteria:

* Pregnancy
* Less than 18 years old
* Terminal cancer patients
* Declined consents
* glucose-6-phosphate dehydrogenase deficiency
* Medication of Serotonin modulator
Breast: Recovery After Axillary Node Clearance - Evaluating Limbs With E-Technology (the BRACELET Study)

This work aims to use wearable sensors to record the return towards normal physical activity after breast surgery. It will build on current evidence by using objective measures of activity and arm movements rather than patient reports.


Eligibility Criteria:
Inclusion Criteria:

* Breast or axillary surgery

Exclusion Criteria:

* Other diagnosed movement disorder
* Cannot consent due to language or capacity
The Relationship of Platelet Micro-RNA Expression and Platelet Reactivity in Patients Under Clopidogrel or Ticagrelor Treatment

For acute coronary syndrome patients undergoing cardiac catheterization after stenting, we will give dual antiplatelet drugs (dual antiplatelet agents) therapy, the choice of the basis of medical criteria (clinical guidelines) routine as aspirin + clopidogrel or aspirin + ticagrelor, according to medical guidelines currently no other disposal alternative proposal (unless adverse drug tolerance or bleeding can not be administered); idea of this experiment for acute coronary syndrome or conventional cardiac catheterization after stenting, platelet miRNA expression (miR-96 , miR-200b, miR-495, miR-107) after cardiac catheterization and interventional treatment of clopidogrel or ticagrelor acceptance of platelet reactivity (PRU) correlation values (given clopidogrel or ticagrelor determined by the clinician, the patient follow-up experiment to track only and observation), aims to explore under different platelet reactivity (hyper-reactive or hypo-reactive), their differences in miRNA performance.


Eligibility Criteria:
Inclusion Criteria:

1 under DAPT (dual antiplatelet therapy) of stable angina patients for elective stent implantation.

2. DAPT 24 hours after treatment PRU (platelet activity units) values. (Drug unresponsive patients was defined as PRU\> 235).

Exclusion Criteria:

1.Not suitable for the treatment of patients with DAPT. (Active peptic ulceration or bleeding) 2 patients of aspirin, clopidogrel, ticagrelor, cilostazol medication intolerance.

3 contraindications for aspirin, clopidogrel, ticagrelor, cilostazol drug usage (such as heart failure patients not suitable for use cilostazol).
The Effect of NOn-invasive Respiratory Support on outcoMe and Its Risks in SARS-COV-2-related Hypoxemic Respiratory Failure

To determine whether early endotracheal intubation compared to late endotracheal intubation affects clinical outcome (duration of invasive mechanical ventilation, mortality).

Non-invasive respiratory support, especially HFNO is usually well-tolerated, especially in COVID-19 patients and can be applied for a prolonged period of time. However, there is a heated debate whether later/delayed endotracheal intubation (due to HFNO / NIV) increases the risk of lung injury, so-called patient self-inflicted lung-injury (P-SILI). The concept of P-SILI assumes that high forces applied to the lung resulting from strenuous breathing effort generated by the patient exacerbates lung-injury and is associated with adverse clinical outcome. It is therefore important to investigate if a longer period of non-invasive respiratory support before invasive mechanical ventilation is associated with adverse clinical outcome. Thus, it is unknown if delaying invasive ventilation worsens clinical outcome. In this study, the research question is whether early compared to late endotracheal intubation improves clinical outcome (duration of invasive mechanical ventilation, mortality)? The aim is to identify the optimal S/F ratio and respiratory rate thresholds for initiating intubation to either improve survival or reduce the duration of invasive ventilation without compromising survival. This is achieved by comparing 25 dynamic treatment regimes defined by combinations of S/F thresholds (\<any, 250, 200, 150, 100) and respiratory rate thresholds (\>any, 16, 20, 25, 30). Thresholds indicating less severe illness (e.g., S/F \< 250 and RR \> 16) are considered 'early intubation,' while thresholds indicating more severe illness (e.g., S/F \< 100 and RR \> 30) are considered 'late intubation'.

Two sensitivity analyses will be conducted:

1. Restricting to patients without hypercapnia (pCO2 \< 45), excluding those with missing pCO2 values or pCO2 \> 45.
2. Including only patients with non-missing Glasgow Coma Scale (GCS) values and adjusting for GCS as a confounder.

Additionally, seven subgroup analyses will be conducted:

1. Patients diagnosed with COVID-19
2. Patients with a history of COPD
3. Patients with a history of CHF
4. Patients with BMI ≤ 30
5. Patients with BMI \> 30
6. Patients on high-flow nasal oxygen (HFNO) at time zero
7. Patients on non-invasive ventilation (NIV) at time zero

Eligibility Criteria:
Inclusion Criteria:

* Hospitalized (inpatient or ICU)
* 18 years or older
* Hypoxemic respiratory failure: S/F\<250
* Not yet intubated

Exclusion Criteria:

* Do not intubate order
* Presence of tracheostomy
COPILOT-HF: Cooperative Program for ImpLementation of Optimal Therapy in Heart Failure

This is a randomized, open-label, initiative within the Mass General Brigham healthcare system testing two remote care strategies for optimizing the prescription of guideline-directed medical therapies in patients with heart failure, regardless of left ventricular ejection fraction (LVEF).

The primary objectives are:

1. Determine if a remote, or virtual, clinic that implements a standardized, stepped-approach to guideline-directed medication optimization in patients with heart failure (across the spectrum of ejection fraction), will achieve a higher rate of guideline-directed medical therapy (GDMT) than a strategy of patient and provider education followed by remote heart failure clinic management.
2. In eligible patients with LVEF\<50%, determine if the sequencing of GDMT initiation (traditional vs. sodium-glucose co-transporter-2 inhibitors-first) leads to improved GDMT intensification

Eligibility Criteria:
Inclusion Criteria:

* Documented diagnosis of heart failure (e.g., ICD-9 codes 428 ICD-10 codes I50 or Problem list in the electronic health record)
* Most recent EF assessed within the past 24 months
* Seen Mass General Brigham provider within the last 24 months
* English or Spanish speaking

Exclusion Criteria:

* LVEF\<50% currently prescribed or intolerant to both ARNi and SGLT2i
* LVEF\>50% currently prescribed or intolerant to SGLT2i
* Systolic blood pressure (SBP) \<90 mmHg at last measure
* Current severe aortic stenosis or severe aortic insufficiency
* Known amyloid heart disease
* Group 1 pulmonary arterial hypertension on disease-specific therapies (e.g., Ambrisentan, Bosentan, Epoprostenol, Treprostinil, Iloprost)
* eGFR\<30 mL/min/1.73m2
* Active chemotherapy
* Receiving end-of-life care or hospice
* History of transplant, currently listed above status 4 or being evaluated for transplant
* Outpatient intravenous inotrope use
* Current use of a Ventricular Assist Device
* Physician's discretion as inappropriate for remote management program
Efficacy of Acupuncture for Chronic Low Back Pain

This is a trial to clarify the extent to which acupuncture needling can diminish the effect of chronic back pain on patient functioning and symptoms.

This is a 4-arm multi-site randomized controlled trial to clarify the extent to which various types of acupuncture needling can diminish the effect of chronic low back pain on patient functioning and symptoms. Reviews have noted the poor quality of research in this area and urged that scientifically rigorous studies be conducted. Recent higher quality trials suggest acupuncture is a promising treatment for back pain. This study directly addresses methodological shortcomings that have plagued previous studies. A total of 640 subjects (160 per arm) with low back pain lasting at least 3 months will be recruited from group model HMOs in Seattle, WA and Oakland, CA. They will be randomized to one of three different methods of stimulation of acupuncture or to continue usual medical care. Ten treatments will be provided over 7 weeks. The primary outcomes, dysfunction and bothersomeness of low back pain, will be measured at baseline, and after 8, 26, and 52 weeks by telephone interviewers masked to treatment. Analysis of covariance within an intention-to-treat context will be used to analyze the data. Because chronic back pain is a major public health problem and the top reason patients seek acupuncture treatment, a clear, unambiguous assessment is critical for making informed decisions about whether acupuncture should be included as part of conventional care for back pain or covered by insurance. Results of this study will provide the clearest evidence to date about the value of acupuncture needling as a treatment for chronic low back pain.

Eligibility Criteria:
Inclusion criteria:

* Diagnosis of low back pain including lumbago, unspecified backache, sprains and strains of sacroiliac, lumbar, sacral, or unspecified regions of the spine
* Back pain must be of at least 3 months duration and rated at least 3 on a symptom bothersomeness scale

Exclusion criteria:

* non-mechanical causes or potential causes of low back pain (i.e. sciatica, underlying systemic or visceral disease, pregnancy, spondylolisthesis, spinal stenosis, cancer or unexplained weight loss, recent vertebral fracture)
* previous treatment with acupuncture
* inappropriate candidate for acupuncture (i.e. severe clotting disorders or on anticoagulant medication, heart pacemakers)
* characteristics complicating the interpretation of the findings (severe or progressive neurologic deficits, back surgery within the prior three years, planning to seek other treatment for back pain)
* characteristics related to ability to complete the study protocol (unable to speak English, plans to move out of town)
Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy

The objective is to determine whether nebivolol, a beta-blockade drug, can prevent the development of heart disease in patients with Duchenne muscular dystrophy aged 10 to 15 year-old.

A 1.25 mg-test dose will be administrated to assess the treatment tolerance before randomization. A forced titration of nebivolol and placebo will be performed with 2 weeks periods. Full dose of nebivolol and placebo is 5mg/day (7.5mg/day for patients whose weight is\>60kg).

Eligibility Criteria:
Inclusion Criteria:

* Duchenne muscular dystrophy genetically proven
* Age between 10 and 15 years
* Left ventricular ejection fraction assessed by radionuclide angiography or echocardiography ≥50% and measured within 3 months
* Systolic blood pressure ≥80 mmHg
* Diastolic blood pressure ≥70 mmHg

Exclusion Criteria:

* Heart rate \<50 bpm
* 2nd or 3rd degree atrioventricular blocks, sinus node dysfunction
* Asthma or bronchospasm
* Severe peripheral circulatory disease
* Hypersensitivity to nebivolol or excipients
* Metabolic acidosis
* Blood urea \>7 mmol/l
* Liver transaminases enzymes \>6 fold the upper limit of normal
* Formal indication for beta-blockade treatment
* Cardiac treatments except angiotensin-converting enzyme inhibitors
* Participation to another clinical trial within 3 months