Featured Studies Open to Enrollment

A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome (LIBREXIA-ACS)

• clinicaltrials.gov

Inclusion Criteria:

• Participants must have an index event that meets all 3 of the following criteria within 7 days prior to randomization:
  • a) clinical syndrome consistent with spontaneous cardiac ischemia, b) diagnosis of acute coronary syndrome (ACS) (that is, ST-elevation myocardial infarction [STEMI], non-STEMI, or unstable angina [UA]), c) cardiac biomarker elevation (example, troponin I, troponin T, creatine kinase-MB [CK-MB]) above the upper limit of normal as determined by the local laboratory
• Participants must have at least 2 of the following risk factors:
  • a) age 65 or older, b) diabetes mellitus, c) history of a prior myocardial infarction (MI) (other than index ACS event), d) multivessel coronary artery disease (CAD), e) history of coronary artery bypass graft (CABG) surgery prior to index ACS event, f) history of peripheral artery disease (PAD) or cerebrovascular disease (example, carotid atherosclerosis, intracranial artery stenosis, g) conservative management (that is, no percutaneous intervention [PCI] or CABG after index ACS event), h) Any one or more of the following high-risk angiographic features i) total stent length of greater than (>) 30 millimeters (mm), ii) thrombotic target lesion, iii) bifurcation lesion treated with more than one stent, iv) calcified target lesion treated with atherectomy, v) treatment of obstructive left main or proximal left anterior descending artery for index ACS (or clinical diagnosis of an anterior STEMI)
• All female participants of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (hCG) or urine test at screening
• A female participant must not be pregnant, breastfeeding, or planning to become pregnant until 4 days (5 half-lives) after the last dose of study intervention

Exclusion Criteria:

• MI secondary to ischemia due to either increased oxygen demand or decreased supply (Type 2 MI) or periprocedural MI as the index ACS event
• Planned CABG or staged PCI after randomization
• Any condition that requires chronic anticoagulation at the discretion of the investigator and/or local guidelines
• Conditions with a significant increased risk of bleeding (example, clinically significant bleeding within previous 3 months, known bleeding diathesis, et cetera)

A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation (LIBREXIA-AF)

Clinicaltrials.gov

Inclusion Criteria:

• Minimum age of 18 years
• Medically stable and appropriate for chronic antithrombotic treatment
• Atrial fibrillation eligible to receive anticoagulation
• Participant must satisfy one or both of the following categories of risk factors (a or b):
  • a) one or more of the following risk factors: i) age greater than or equal to 75 years, ii) history of any type of stroke including symptomatic stroke of any kind.
  • b) two or more of the following risk factors: i) age between 65 and 74 years, ii) hypertension, iii) diabetes mellitus, iv) atherosclerotic vascular disease, v) heart failure

Exclusion Criteria:

• Hemodynamically significant valve disease or those with valve disease that will potentially require surgical valve replacement during the study
• Any condition other than AF that requires chronic anticoagulation

A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack- (LIBREXIA-STROKE)

• Clinicaltrials.gov

Inclusion Criteria:

• Ischemic Stroke: a neurological deficit attributable to an acute brain infarction and national institute of health stroke score scale (NIHSS) score less than or equal to (<=) 7 and at least 1 of the following: persistent signs or symptoms of the ischemic event at the time of randomization, or acute, ischemic brain lesion determined by standard-of-care neuroimaging, or participant underwent thrombolysis or thrombectomy, or transient ischemic attack (TIA): acute onset neurological deficit attributable to focal ischemia of the brain by history or examination, with complete symptom resolution of the deficit and no brain infarction on neuroimaging (example, computed tomography (CT) scan or magnetic resonance imaging (MRI), performed as part of standard medical practice), and ABCD2 Score greater than or equal to (>=)
• Participants will be randomized as soon as possible after determining eligibility and within 48 hours of onset of event.
• Current or planned antiplatelet treatment per international and/or local guidelines. If acetyl salicylic acid (ASA) is used, it will be limited to low dose (75 to 100 milligrams (mg)/day). Loading dose of antiplatelet agents (including ASA) are allowed per standard-of-care
• A female participant must agree not to be pregnant, breastfeeding, or planning to become pregnant until 4 days (5 half lives) after the last dose of study intervention
• Willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion Criteria:

• Prior history of intracranial hemorrhage except subarachnoid hemorrhage greater than (>) 1 year prior with adequate treatment
• The index stroke or TIA is considered to have a cardio-embolic etiology based on local standard-of-care investigations and for which guidelines recommend anticoagulation
• The index stroke or TIA considered to have another known cause, not related to athero-thrombotic sources (treatment of acute stroke trial [TOAST] Other Determined Etiology), based on local standard-of-care investigations
• Increased risk of bleeding, including clinically significant bleeding within the previous 3 months or known bleeding diathesis or known activated partial thromboplastin time (aPTT) prolongation or spinal cord hemorrhage or retinal hemorrhage
• Current active liver disease, eg, acute hepatitis, known cirrhosis, including participants receiving antiviral treatment for hepatitis
• Known allergies, hypersensitivity, or intolerance to milvexian or its excipients

LIMIting AAA with metformin

• Clinicaltrials.gov 

Inclusion Criteria:

• Provision of signed and dated informed consent
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 50 to 95 years inclusive
• Have a maximal orthogonal infrarenal aortic diameter between 35 and < 50 mm for males and between 30 and < 45 mm for females as measured by CTA
• Eligible participants must have an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2 at the initiation of trial participation, and must remain ≥ 30 ml/min/1.73 m2 throughout the term of the study to continue participation
• HgbA1c must be ≤ 6.5% at initiation to receive study medication
• Ability to take oral medication and be willing to adhere to the medication regimen throughout the course of the trial
• Must be willing and able to undergo two computed tomographic aortograms (CTA, with timed intravenous iodinated contrast injections if possible) at initiation and termination of study participation
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening, with an agreement to use such a method of contraception during study participation and for an additional 4 weeks after the end of study drug administration

Exclusion Criteria:

• Diagnosis of, or taking medications for, diabetes mellitus, as defined as HgbA1c > 6.5% at baseline evaluation
• Known hypersensitivity to metformin hydrochloride. Individuals with known prior anaphylactic reaction to iodinated contrast will have the option of CT scan without contrast or will not be eligible to participate. Individuals with a prior allergic reaction not including anaphylaxis will be managed with the standard CT protocol for premedication for allergy to contrast – 3 doses of prednisone (50 mg p.o. per) beginning 13 hours prior to the procedure as well as 50 mg of Benadryl p.o. Premedication start times are as follows: 13 hours before contrast, 50 mg PO prednisone 7 hours before contrast, 50 mg PO prednisone 1 hour before contrast, 50 mg PO prednisone + 50 mg PO diphenhydramine These individuals will also be given the option of CT scan without contrast if unwilling to follow the premedication as indicated above
• Presence of metabolic acidosis, defined as total CO2 below the lower limit of normal on chemistry panel obtained during determination of study eligibility
• Expected survival less than two years
• Prior surgical AAA repair, or anticipated repair within two years
• Known thoracic aortic aneurysm disease, as defined as a prior dissection or thoracic aortic diameter > 5 cm)
• The presence of known syndromic aortic conditions, including but not limited to Ehlers Danlos or Marfan Syndromes, or the at-risk allele in the ACTA2 gene mutation or similar conditions
• Severe liver disease, jaundice, or active hepatitis
• Severe anemia, defined as a Hgb < 10g/dl
• Concurrent participation in other investigational drug trials
• For female participants of childbearing potential: pregnancy, intent to become pregnant, lactation, or unwilling or unable to use an effective method of contraception
• Alcoholism or chronic excessive alcohol intake
• Common iliac artery aneurysms > 3.5 cm
• Uncontrolled hypertension defined as Systolic BP≥200, or considered to have hypertensive emergency or urgency

Food Insecurity Reduction & Strategy Team (FIRST)

• clinicaltrials.gov

Inclusion Criteria:

• Diagnosis of Type 1 or Type 2 Diabetes Mellitus
• Admitted to Stanford Healthcare inpatient unit
• Residence in California at time of enrollment
• Positive Screening for Food Insecurity
• On a Healthcare Plan covered by Mom’s Meals.

Exclusion Criteria:

• Plans to be discharged to a skilled nursing facility.
• Patients who prefer a language for which a short-form consent is not available.
• No Home Address
• Pregnant Participants.
• No access to refrigerator.

A Phase 2 Study of VLX-1005 Versus Placebo in Suspected Heparin Induced Thrombocytopenia

• clinicaltrials.gov

Inclusion Criteria:

• Adult participants ≥ 18 years of age.
• Able to provide informed consent or have informed consent provided on their behalf by a primary caregiver prior to study-related activities being initiated.
• Recent unfractionated heparin or low-molecular-weight heparin exposure.
• Qualifying platelet count < 150 X 10^9/L and clinical 4T score of ≥ 4; candidate for argatroban or bivalirudin treatment.
  Positive PF4-immunoassay (eg, ELISA [≥ 1.0 optical density units], LIA [≥ 1.0 U/mL], CLIA [≥ 1.0 U/mL]).

Exclusion Criteria:

• Treatment with argatroban or bivalirudin for ≥ 60 hrs prior to randomization.
• Following discontinuation of heparin, participants cannot be treated with a non-heparin anti-coagulant for ≥ 60 hours.
• Current renal dialysis.
• Pregnant or lactating women.
• Have participated in any other investigational drug trial within 30 days of dosing or 5 half-lives (whichever is longer) in the current study.
• In the opinion of the investigator, unlikely to comply with key elements of the protocol or otherwise inappropriate for the study.

PEMSCOPE: Pathobiology of Post-Exertional Malaise in SARS-CoV-2: A Prospective Clinical Cohort Study in a
Quest for a Biomarker

CASES
Inclusion criteria for long COVID participants*

1. Adults 18 years and older
2. Weight > 40 Kg
3. Normal or near-normal renal function (eGFR ≥60 ml/min)
4. History of confirmed COVID-19 infection (Self-reported from at home test, SARS-CoV-2 positive PCR/NAAT, positive antigen, positive nucleocapsid antibodies, or positive spike antibodies before vaccination for SARS-CoV-2), preceding COVID-19 symptoms and the symptoms persisted > 12 weeks at the time of enrolment in the study
5. Fit DQS-PEM Score [1]

*If has an abnormal ECG, pulmonary function testing (PFT), Chest X-ray, and echocardiogram, inclusion/exclusion will be at the discretion of the protocol investigator.

CONTROLS
Inclusion criteria COVID-19 recovered participants

1. Adults 18 years and older
2. Weight > 40 Kg
3. Normal or near-normal renal function (eGFR ≥60 ml/min)
4. History of confirmed COVID-19 infection (Self-reported at home test, SARS-CoV-2 positive PCR/NAAT, positive antigen, positive nucleocapsid antibodies, or positive spike antibodies before vaccination for SARS-CoV-2 > 12 weeks at the time of enrolment in the study
5. Full recover to the baseline before the infection
6. No contraindication for CPET

Inclusion criteria for the sub study regardless of the cohort:

1. Current consented subject in the parent PEM-scope clinical trial
2. Adult ≥ 18 years of age
3. Able and willing to provide written informed consent for the study
4. Able and willing to comply with all study procedures
5. Able to read and speak English
6. Currently owns Apple iPhone 6S or higher with a data plan and is the sole user of that iPhone and/OR Apple iPad with WiFi connectivity
7. Agrees to download and maintain the AiCare and Welch Allyn App onto iPhone or iPad for the duration of the substudy.

Exclusion criteria.CASES
Exclusion criteria for long COVID participants*

1. Pregnant or breastfeeding
2. Medical condition that explains current symptoms
3. Acute coronary heart disease
4. Acute myocarditis/pericarditis
5. Syncope
6. Congestive heart failure
7. Pulmonary edema
8. Valvular heart disease
9. Uncontrolled hypertension
10. Oxygen Saturation less than 94%
11. Uncontrolled thyroid disease
12. Renal failure (Creatinine Clearance < 60)
13. Anemia
14. Acute infection (Fever/temperature 98.6 F, urinary tract infection, respiratory, skin, etc)

*If has an abnormal ECG, pulmonary function testing (PFT), Chest X-ray, and echocardiogram, inclusion/exclusion will be at the discretion of the protocol investigator.

CONTROLS
Exclusion criteria COVID-19 recovered participants

1. Pregnant or breastfeeding
2. Medical conditions that limit exercise
3. Acute coronary heart disease
4. Acute myocarditis/pericarditis
5. Syncope
6. Congestive heart failure
7. Pulmonary edema
8. Valvular heart disease
9. Uncontrolled hypertension
10. Oxygen Saturation less than 94%
11. Uncontrolled thyroid disease
12. Renal failure (CrCl < 60)
13. Anemia
14. Acute infection (Fever/temperature 98.6 F, urinary tract infection, respiratory, skin, etc)

Exclusion criteria for sub-study regarless of the cohort:

1. Unable to provide written informed consent
2. Known hypersensitive skin, allergies to wristbands of similar product, or severe allergy to nickel or metal jewelry”

ReSPECT: Study of Rezafungin Compared to Standard Antimicrobial Regimen for Prevention of Invasive Fungal Diseases in Adults Undergoing Allogeneic Blood and Marrow Transplantation

• clinicaltrials.gov

Inclusion Criteria:

• Willing and able to provide written informed consent.
• Males or females ≥18 years of age.
• Receiving a human leukocyte antigen (HLA) matched allogeneic peripheral BMT from a family or unrelated donor, HLA-mismatched related or unrelated donor, or haploidentical donor.

Diagnosed with 1 of the following underlying diseases:

• Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission.
• Acute lymphoblastic leukemia, in first or second complete remission.
• Acute undifferentiated leukemia in first or second remission.
• Acute biphenotypic leukemia in first or second complete remission.
• Chronic myelogenous leukemia in either chronic or accelerated phase.

One of the following myelodysplastic syndrome(s) defined by the following:

• Refractory anemia.
• Refractory anemia with ringed sideroblasts.
• Refractory cytopenia with multilineage dysplasia.
• Refractory cytopenia with multilineage dysplasia and ringed sideroblasts.
• Refractory anemia with excess blasts – 1 (5-10% blasts).
• Refractory anemia with excess blasts – 2 (10-20% blasts).
• Myelodysplastic syndrome, unclassified.
• Myelodysplastic syndrome associated with isolated del (5q).
• Lymphoma (including Hodgkin’s) with chemosensitive disease (i.e., response to chemotherapy) and receiving a related or unrelated donor transplant.
• Aplastic anemia.
• Primary or secondary myelofibrosis.
• Chronic myelomonocytic leukemia.
• Chronic lymphocytic leukemia.
• Drepanocytosis (sickle cell anemia).
• Red blood cell aplasia.
• Myeloproliferative disorder, unclassified.
• Multiple myeloma (plasma cell myeloma).
• Receiving myeloablative or reduced-intensity conditioning regimens.

Adequate renal and hepatic function prior to initiation of conditioning regimen, therefore between 40 days prior and 10 days prior to BMT, documented as follows:

• Hepatic: alanine aminotransferase less than or equal to (≤) 2.5 × upper limit of normal (ULN) and total serum bilirubin ≤1.5 × ULN (excluding Gilbert’s Syndrome).
• Renal: serum creatinine ≤2 milligrams (mg)/deciliter (dL) and with creatinine clearance (CrCl) greater than or equal to (≥) 30 milliliters (mL)/minute (min) without a history of renal transplant, or undergoing weekly dialysis within 4 weeks of the BMT.
• Baseline blood samples drawn for Platelia galactomannan enzyme immunoassay (GM EIA) and β-D glucan levels within 15 days before randomization, with results available prior to randomization.
• Baseline Toxoplasma serologies available within 6 weeks prior to randomization. Subjects with a positive toxoplasma IgG serology at any time prior to randomization do not need to repeat the toxoplasma serologies (IgG and IgM) and will be considered to have a prior history of toxoplasmosis.
• Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency determination by the investigator prior to randomization with no known evidence of G6PD deficiency performed any time prior to randomization. If the Investigator assesses the subject as G6PD sufficient, the G6PD test result does not need to be entered into the EDC system.
• Female subjects of child-bearing potential <2 years post-menopausal (unless surgically sterile) must agree to and comply with using 1 barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence (only possible if it corresponds to the subject’s usual lifestyle) while participating in this study, and for 30 days after the last dose of study drug. Male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception (condom with spermicide), and agree not to

Arctic – AstraZeneca: A Phase III, Randomised, Double -Blind, Active-controlled Study to Assess the Efficacy, Safety and Tolerability of Baxdrostat in Combination with Dapagliflozin Compared with Dapagliflozin Alone on Chronic Kidney Disease (CKD) Progression in Participants with CKD and High Blood Press

• clinicaltrials.gov

Inclusion Criteria:

• Participants of any sex and gender must be ≥ 18 years old, or older, at the time of signing the informed consent.
• Participants with CKD and eGFR ≥ 30 and < 90 mL/min/1.73 m2 at screening
• Urine albumin creatinine ratio > 200 mg/g (22.6 mg/mmol) and < 5000 mg/g (565 mg/mmol) at screening
• Participants with history of HTN and a SBP ≥ 130 mmHg at screening and ≥ 120 mmHg at the randomisation visit
• Stable and maximum tolerated dose of an ACE inhibitor or an ARB (not both) for at least 4 weeks prior to Screening Visit

Central laboratory serum potassium must meet the following criteria at the Screening Visit, based on screening eGFR:

• for participants with screening eGFR ≥ 45 mL/min/1.73 m2, potassium must be ≥ 3.5 and ≤ 4.8 mmol/L at the Screening Visit
• for participants with screening eGFR < 45 mL/min/1.73 m2, potassium must be ≥ 3.5 and ≤ 4.5 mmol/L at the Screening Visit

Exclusion Criteria:

• Systolic blood pressure > 180 mmHg, or DBP > 110 mmHg at screening.
• Known hyperkalaemia, defined as potassium of ≥ 5.5 mmol/L within 3 months at screening.
• Serum sodium < 135 mmol/L at the Screening Visit, determined as per central laboratory.
• Type 1 diabetes mellitus or uncontrolled Type 2 diabetes mellitus with HbA1c > 10.5% (> 91 mmol/mol) at Screening.
• New York Heart Association functional HF class IV at screening.
• Stroke, transient ischaemic cerebral attack, valve implantation or valve replacement, carotid surgery, or carotid angioplasty, acute coronary syndrome, or hospitalisation for worsening heart failure within previous 3 months prior to randomisation.
• Any dialysis (including for acute kidney injury) within 3 months prior to Screening Visit.
• Any acute kidney injury within 3 months prior to the Screening Visit
• History of organ transplant or bone marrow transplant, or planned organ transplant within 6 months following randomisation (including kidney transplant).
• History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2 inhibitor (eg, empagliflozin) or ASI.
• Any clinical condition requiring systemic immunosuppression therapy other than stable maintenance therapy for at least 3 months prior to Visit 1.
• Any use of mineralocorticoid receptor antagonists (such as spironolactone, eplerenone, or finerenone), potassium-sparing diuretics (such as triamterene or amiloride), or potassium binders (such as sodium zirconium cyclosilicate, patiromer, or sodium polystyrene sulfonate) within 4 weeks prior to screening.

Developing Tools for Dialysis Decision Support – Online Dialysis Decision

• clinicaltrials.gov

Inclusion Criteria:

• Age >=65
• Estimated GFR ;25 ml/min/1.73m2
• English speaking
• Not a candidate for kidney transplant based on nephrologist assessment.

Family/caregiver inclusion criteria:

• Age <=21
• English speaking

Exclusion Criteria:

• Patients with cognitive impairment will be excluded; however their family member or caregiver is eligible to participate.

PAS-SSD: Investigation to Evaluate the Safety and Effectiveness of Cochlear Implantation in Children and Adults With Unilateral Hearing Loss/​Single-sided Deafness

• clinicaltrials.gov

Inclusion Criteria:

• Individuals 18 years or older (Group A)
  • Ear to be Implanted:
    • Severe sensorineural hearing loss (HL) defined as: Pure-tone average at 0.5, 1, 2, 4 kHz >80 dB HL ; Aided Consonant-Nucleus-Consonant Test (CNC) score ≤5% and
  • Normal Hearing Ear:
    • Normal or near normal hearing defined as an average of (0.5, 1, 2, 4kHz) ≤ 30 dB HL
• Children 5 years to 17 years, 11 months (Group B)
  • Ear to be Implanted:
    • Severe sensorineural HL defined as: Pure-tone average at 0.5, 1, 2, 4 kHz >80 dB HL; Aided CNC score ≤5% and
  • Normal Hearing Ear:
    • Normal or near normal hearing defined as an average of (0.5, 1, 2, 4kHz) ≤ 30 dB HL
• Previous experience with a current conventional treatment option for unilateral [SSD] HL (HA, bone-conduction device, or CROS technology), if no previous experience a minimum trial period of two weeks is required
• English spoken as a primary language
• Willing and able to provide written informed consent

Exclusion Criteria:

• Ossification, abnormal cochlear nerve or any other cochlear anomaly that might prevent complete insertion of the electrode array
• Previous cochlear implantation
• Hearing loss of neural or central origin, including auditory neuropathy
• Duration of profound sensorineural HL >10 years per self-report
• Active / chronic middle-ear infection; conductive HL in either ear
• Medical or psychological conditions that contraindicate undergoing surgery as determined by the Investigator
• Unrealistic expectations on the part of the participant/family, regarding the possible benefits, risks, and limitations that are inherent as determined by the Investigator
• Evidence of and/or suspected cognitive or developmental concern
• Unable or unwilling to comply with the requirements of the clinical investigation as determined by the Investigator
• Investigator site personnel directly affiliated with this study and/or their immediate families; immediate family is defined as a spouse, parent, child or sibling
• Cochlear employees or employees of Contract Research Organizations (CROs) or contractors engaged by Cochlear for the purposes of this investigation
• Pregnant or breastfeeding women
• Currently participating, or participated within the last 30 days, in another interventional clinical investigation/trial involving an investigational drug or device.

Arrest RESpiraTory Failure From Pnemonia

• Clinicaltrials.gov

Inclusion Criteria:

• Patients 18 years or older with
• Severe pneumonia defined as: Hospitalization for acute (defined as ≤ 14 days) onset of symptoms (cough, sputum production, or dyspnea), AND 2. Radiographic evidence of pneumonia by chest radiograph or CT scan, AND 3. One of the following:
  • Evidence of systemic inflammation (temperature < 35◦C or > 38◦C OR WBC > or < upper or lower limits for site OR procalcitonin > 0.5 mcg/L), OR
  • Known current immunosuppression preventing inflammatory response, OR
  • High clinical suspicion of pneumonia with microbiologic confirmation of infection. Microbiologic confirmation will include a positive nasal swab for a known respiratory virus; a sputum culture growing a likely pathogenic organism plus moderate or greater WBCs (not required for immunocompromised patients); or a positive blood culture with a likely pathogenic organism – e.g., ¼ vials with S. Epidermidis would NOT qualify)
  • AND Hypoxemia defined as new requirement for daytime supplemental oxygen with SpO2 < 92% on room air, ≤ 96% on ≥ 2 L/min oxygen, or > 6L/min or non-invasive ventilation regardless of SpO2 at enrollment. Patients admitted with pneumonia but not meeting criteria for hypoxemia will be followed for up to 48 hours from ED admission to enrolling hospital to assess for development of qualifying hypoxemia

Exclusion Criteria:

• Inability to randomize within 48 hours of presentation to enrolling hospital (randomization beyond 24 hours will be limited to patients with persistent hypoxemia defined by an SpO2 < 97% while on > 3L/min O2)
• Intubation (or impending intubation) prior to enrollment
• Patients receiving HFNC oxygen or NIV prior to enrollment are not excluded
  • A condition requiring inhaled corticosteroids or beta-agonists (patients receiving inhaled beta-agonists in the ED without an established indication will be eligible if treating clinician is willing to discontinue subsequent treatments)
  • Chronic systemic steroid therapy equivalent to >10 mg prednisone
  • COVID-19 positive patients receiving > 6 mg dexamethasone (40 mg prednisone equivalent dose) except for stress dose steroids for septic shock
  • Non-COVID-19 pneumonia patients receiving systemic steroid > 10 mg prednisone except for stress dose steroids for septic shock
  • Chronic lung or neuromuscular disease requiring daytime oxygen or mechanical ventilation other than for obstructive sleep apnea (OSA) or obesity hypoventilation syndrome
  • Not anticipated to survive > 48 hours or not expected to require > 48 hours of hospitalization
  • Contraindication or allergy to inhaled corticosteroids or beta-agonists
  • Patients with heart rate > 130 bpm, ventricular tachycardia or new supraventricular tachycardia within last 4 hours will be potentially eligible for enrollment after the condition has resolved
  • Patients with K+ < 3.0 will be potentially eligible for enrollment after the condition has resolved
  • Patient not committed to full support other than intubation or resuscitation (i.e., DNR/DNI status allowed)
  • Pregnancy
  • Incarcerated individual
  • Physician refusal of consent to protocol
  • Patient/surrogate refusal of consent to protocol

RECOVER-AUTONOMIC: A Platform Protocol for Evaluation of Interventions for Autonomic Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection

clinicaltrials.gov

Inclusion Criteria:

• ≥ 18 years of age at the time of enrollment
• Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization12ɸ ɸ Enrollment of participants with suspected or probable SARS-CoV-2 infection will only be allowed if they occurred before May 1, 2021 and be limited to no more than 10% of the total sample size per Study Drug Appendix. Refer to the Manual of Procedures (MOP) for details.
• Suspected case of SARS-CoV-2 infection – Three options, A through C:
• A. Meets the clinical OR epidemiological criteria.
  Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia.
• Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presents with acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization); or C. Presents with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-Rapid Diagnostic Test.
• Probable case of SARS-CoV-2 infection, defined as meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster.
• Confirmed case of SARS-CoV-2 infection – Two options, A through B:
• A. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. Meeting clinical criteria AND/OR epidemiological criteria (See suspect case A). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.
• Moderate, self-identified autonomic symptoms (defined as COMPASS-31 >25) following a SARS-CoV-2 infection that has persisted for at least 12 weeks and is still present at the time of consent
• OHQ/OIQ, question 1 score >2

Exclusion Criteria:

• Known pregnancy, breast-feeding, or contemplating pregnancy during the study period
• Known active acute SARS-CoV-2 infection ≤ 4 weeks from enrollment
• Known renal failure (eGFR <20ml/1.73 m²)
• Known atrial fibrillation or significant cardiac arrhythmia
• Known cardiovascular conditions such as heart failure (Class 3-4), severe valvular disease, symptomatic ischemic coronary artery disease, revascularization for PAD/CAD within the past 6 months
• Clinically significant atherosclerotic disease, defined as history of stroke or myocardial infarction or revascularization 6 months prior to enrollment and/or current symptomatic angina
• Existing uncontrolled hypertension
• History of significant hypercoagulability disorders
• Active or recent thrombosis