The alfapump® system is currently not approved in the United States or Canada. In the United States and Canada, the alfapump® system is currently under clinical investigation (POSEIDON Study) and is being studied in adult patients with refractory or recurrent ascites due to cirrhosis. DSR® therapy is still in development and it should be noted that any statements regarding safety and efficacy arise from ongoing pre-clinical and clinical investigations which have yet to be completed. There is no link between the DSR® therapy and ongoing investigations with the alfapump® system in Europe, the United States or Canada.
This is a randomized controlled Phase 1/2a study in the US, that will evaluate the safety and efficacy of DSR 2.0 in diuretic-resistant chronic heart failure patients with persistent congestion.
The study commences with a non-randomized cohort of three eligible patients treated with DSR 2.0, administered via a peritoneal dialysis (PD) catheter, on top of optimized usual care for congestive heart failure for up to four weeks followed by a three-month safety follow-up period. Progress to the multi-center randomized cohort of up to 30 additional patients depends on approval from the Data and Safety Monitoring Board (DSMB) following review of the non-randomized cohort data.
The randomized cohort will consist of up to 20 randomized patients treated with DSR 2.0, administered via a PD catheter, on top of optimized usual care for congestive heart failure for up to four weeks and up to ten randomized patients treated with intravenous loop diuretics alone as part of maximized usual care for congestive heart failure. Following four weeks of treatment, there is a three-month safety follow-up period.
Primary and secondary safety and efficacy endpoints include the rate of adverse and serious adverse events and the improvement in diuretic response (measured as a six-hour urine sodium output) from baseline through the end of the treatment period. Exploratory endpoints measured from baseline through the end of the treatment period include change in weight (volume status), creatinine (a marker of renal function), natriuretic peptides (a marker of heart failure) and New York Heart Association (NYHA) functional class; and the number of heart failure related rehospitalizations.
SAHARA – REPEATED DOSE DSR STUDY IN DECOMPENSATED HEART FAILURE PATIENTS
SAHARA is a multi-centre, prospective, randomised, open-label study to evaluate the safety and feasibility of DSR therapy in heart failure patients with persistent congestion and resistance to loop diuretic treatment. Patients will undergo a diuretic challenge to quantify their response to diuretics, which will be repeated at specific time points throughout the study. At the start of the study treatment period, loop diuretics will be withheld and patients will be randomised 1:1 to DSR therapy with or without SGLT2-inhibitor to evaluate their impact on DSR therapy. Patients will undergo intensive DSR therapy with DSR D10% infusate for two weeks (phase 1) which can be repeated up to two times depending on their euvolemic state, diuretic response and stable DSR dosing at the end of phase 1. Patients who have achieved euvolemia and have adequate diuretic response will enter into the maintenance DSR treatment phase with monthly DSR dosing for 16 weeks (phase 2).
The primary safety and tolerability endpoints include the rate of treatment-, device- or procedure-related serious adverse events through the end of the maintenance phase. Secondary feasibility endpoints include the ability of DSR therapy to restore and maintain euvolemia without the need for additional loop diuretic treatment. Additional exploratory endpoints will evaluate the potential impact of SGLT-2 inhibitors on DSR therapy. The study is being conducted in up to three clinical centres in the Republic of Georgia. For more information about the study, please visit clinicaltrials.gov (NCT04882358).
Positive top-line results SAHARA:
Press release 15 November 2022
RED DESERT – REPEATED DOSE DSR STUDY IN HEART FAILURE PATIENTS ON HIGH DOSE DIURETICS
Prospective, single-arm, first-in-human repeated dose study to evaluate the safety and feasibility of DSR in diuretic-resistant heart failure patients. Results demonstrated that repeated DSR therapy could effectively replace patients’ high dose loop diuretics and restore their diuretic response and overall cardio-renal status. These strong results were presented at the Heart Failure 2021 Digital Congress as part of the Late Breaking Science Results and selected for the congress’ Highlights session.
Presentation by Dr. Testani at THT 2022
Presentation by Dr. Testani at Heart Failure 2021
Abstract “First in Human Experience with Alfapump DSR System in Diuretic Resistant Chronic Heart Failure”
Webcast by Sequana Medical management on 11 May 2021
DSR® CLINICAL PROOF OF CONCEPT STUDY
First-in-human single dose DSR® proof of concept study to assess safety, tolerability and impact of direct sodium removal therapy in 10 patients receiving peritoneal dialysis (PD). Results selected for late-breaking abstract session at Heart Failure 2019.
Testani et al., Circulation, 2019
Presentation by Dr. Testani at Heart Failure 2019
Webcast by Sequana Medical management and Dr. Testani on 27 May 2019
DSR® PRECLINICAL PROOF OF CONCEPT STUDY
Single dose, single arm preclinical proof of concept study to assess impact of direct sodium removal therapy in 15 healthy pigs and 5 pigs with experimentally induced heart failure via tamponade.
Poster by Testani et al., HFSA, 2018