Clinical trial NCT06554912: FLOWS-HF : Feasibility of Lymphatic Offloading with Stenting in Heart Failure
Official title: Evaluation of Safety and Feasibility of Lymphatic Decompression in Chronic Heart Failure
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Cardiovascular Diseases
Chronic Heart Failure
Keywords: Lymphatic Decompression
Chronic Heart Failure
Stenting
Lymphatic system
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Selera Medical
First posted: 2024-08-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The main objective is to evaluate the safety of lymphatic decompression in heart failure.

The research hypothesis is that lymphatic decompression is safe and feasible in heart failure patients with recurrent congestion despite on maximum tolerated diuretic dosage. Safety will be evaluated by the rate and severity of adverse events. Feasibility will be assess based on procedural success and time.

In demonstrating that this approach is both safe and feasible, the expected benefits of the research include symptom relief for patients as well as data generation and considerations for a novel treatment for chronic heart failure patients. Ultimately, this research will contribute to the development of an additional treatment option for patients that remain congested while on standard-of-care therapies.

Detailed description: Better understanding of the lymphatic system's role in managing volume status and how this system is overwhelmed in HF has made it a compelling target for intervention. Historic and contemporary preclinical and clinical evidence demonstrate that surgically relieving or bypassing the resistance at the LVJ when the lymphatic system is overwhelmed significantly improves volume status in heart failure. Although it demonstrates clinical benefit in a majority of patients, the surgical approach has greater risks and is not scalable due to technical difficulties. More recently, improved clinical outcomes and feasibility of minimally invasive lymphatic decompression via transcatheter thoracic duct stenting was demonstrated in cirrhosis, another volume-overload related condition. With supportive preclinical and clinical data, this study aims to evaluate lymphatic decompression in heart failure.

Eligibility criteria: Inclusion Criteria:

* Subjects ≥18 years of age
* Diagnosis of chronic heart failure (reduced or preserved EF) with evidence of diastolic dysfunction on echocardiogram
* Chronic NYHA class II or greater
* Prone to cardiorenal syndrome or refractory to diuretics (e.g. on lasix 125 mg PO total daily dose or equivalent diuretic dosing for 1 or more months prior to enrollment)
* History of symptoms of congestion (e.g. dyspnea, peripheral edema, pleural effusion, and/or ascites) in preceding 12 months requiring HF hospitalization with IV diuresis
* NT-proBNP \>1000 pg/ml
* eGFR \> 20 ml/min/1.73m2
* Life expectancy \> 6 months
* Membership of the social security system or benefiting from such a system
* Able and willing to sign informed consent

Exclusion Criteria:

* Anatomy not considered suitable based on CT with contrast (e.g., not visible, multiple terminal ducts or plexiform termination)
* Other cause of thoracic duct congestion based on CT with contrast (superior cava vein/left brachiocephalic vein/ jugular or subclavian vein thrombosis)
* Acute coronary syndrome, stroke, pulmonary embolism in previous 6 months
* Stage IV or stage V chronic kidney disease, or end-stage renal disease (ESRD) requiring dialysis, or severe renal failure (\<30ml/min)
* Cardiac surgery within past 6 months (coronary artery bypass grafting, valvular, or pericardial surgery)
* Transcatheter structural heart intervention within past 6 months
* Active pregnancy, breastfeeding, or anticipated pregnancy within 1 year
* Known coagulation disorders or inability to take blood thinning medications (anticoagulation or antiplatelet therapy) for at least one month after procedure
* Severe pulmonary hypertension (RVSP \>60mmHg as assessed by echocardiogram)
* Severe RV dysfunction (TAPSE \<17mm, RFAC \<35%)
* Known allergies or sensitivities to materials utilized in procedure, including contrast agents
* Candidate deemed unsuitable based on investigator opinion
* Subject in exclusion period of another study
* Subject under administrative or judicial supervision
* Subject unable to provide informed consent

Primary outcomes:
measure: Evaluation of the lymphatic decompression's safety in heart failure by the assessment of the rate and severity of adverse events after the procedure of thoracic duct decompression.
timeFrame: During 180 days after the procedure +/- 4 days
Secondary outcomes:
measure: Evaluation of the lymphatic decompression's feasibility in heart failure
timeFrame: Procedure day (D0-1)
measure: Evaluation of the lymphatic decompression's feasibility in heart failure
timeFrame: Procedure day (D0-1)
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (urine output)
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (sodium output)
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (medication dosing requirements).
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (KCCQ quality of life score)
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (EVEREST congestion score)
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (6-min walk test)
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (number of heart failure hospitalization)
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (IV diuresis rates)
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (frequency of paracentesis)
timeFrame: During 180 days after the procedure +/- 4 days
measure: To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (frequency of thoracentesis)
timeFrame: During 180 days after the procedure +/- 4 days
measure: Evaluation of the lymphatic decompression's impact on thoracic duct pressure
timeFrame: Before the procedure and days 90 +/- 4 days after the procedure
measure: Evaluation of the lymphatic decompression's impact on central hemodynamic functions. (Blood flow dynamics in mmHg).
timeFrame: Days 30, Days 90 and days 180 after the procedure
measure: Evaluation of the lymphatic decompression's impact on renal function
timeFrame: Days 30, Days 90 and days 180 after the procedure
Other outcomes:
Locations:
Study officials:
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