Slide 1: First in human experience with direct sodium removal using a zero sodium peritoneal solution
First in human experience with direct sodium removal using a zero sodium peritoneal solution: A new candidate therapy for volume overload Veena Rao, Jeffrey Turner, Devin Mahoney, Matthew Griffin, Jennifer Asher, Juan Ivey-Miranda, Nicole Gomez, Fredric Finkelstein, Jeffrey Testani Jeffrey M. Testan
Slide 2: Disclosures
Disclosures • Related to the presentation: Research funding and consulting fees from Sequana Medical • Unrelated to the presentation: Grants and consulting fees from BMS, consulting fees from AstraZeneca, consulting fees from Novartis, grants and consulting fees from 3ive Labs, consulting fees from
Slide 3: Heart Failure: Can we do better than diuretics?
Heart Failure: Can we do better than diuretics? • On a population level, symptoms and hospitalizations are driven by volume overload – Loop diuretics are the mainstay of therapy – Well described toxicity – Resistance is common • Long list of failed cardio-renal therapeutics has accumulated over the
Slide 4: Why is peritoneal dialysis (PD) not used more frequently in heart failure?
Why is peritoneal dialysis (PD) not used more frequently in heart failure? • Standard PD has several limitations: – Large volumes (~8 to 10 liters) and long dwell times with the patient connected to PD cycler – External catheter with infection risks – Dialysis stigma • Only modest fluid and sodium r
Slide 5: Can we use the peritoneal membrane more efficiently to directly remove sodium in HF patients?
Can we use the peritoneal membrane more efficiently to directly remove sodium in HF patients? • Most HF patients have acceptably functioning kidneys • No need to “clean” the blood • Standard PD solutions have ~7.5 grams of salt per liter • Nearly isotonic to plasma (~132 mmol/L) • Very small gradien
Slide 6: Pre-clinical data: Results in normal swine
Pre-clinical data: Results in normal swine • 1 Liter of sodium free 10% dextrose in water as the Direct Sodium Removal (DSR) solution • 6 hour dwell: (n=4) • 2 hour dwell (N=10): – 5.5 grams of sodium – 3.9 grams of sodium – 1.5L of ultrafiltrate – 800 cc of ultrafiltrate 6 5 5 4 Sodium (g) 4 Sodium
Slide 7: Pre-clinical data: Heart Failure vs. normal pigs
Pre-clinical data: Heart Failure vs. normal pigs • Right sided HF model with fluid loading and tamponade • 2 hour DSR dwell CVP (mmHg) Pericardial Pressure (mmHg) 20 p < 0.0001 30 15 15 Sodium (g) CO (L/min) 20 10 mmHg 10 10 5 Cardiac Output (L/min) 5 0 0 Pre- Post- Post- 30 min 60 min 90 min 120 mi
Slide 8: DSR first in human proof of concept: Design
DSR first in human proof of concept: Design • Design: – Randomized open label crossover of DSR vs. standard PD solution – Conducted in prevalent PD patients rather than normal subjects due to the risks of PD catheter placement • Intervention: – DSR solution: Sodium free 10% dextrose – Standard PD so
Slide 9: Primary endpoint: Safety and tolerability
Primary endpoint: Safety and tolerability • Primary endpoint: – All patients completed the 2 hour dwell without adverse event or significant discomfort causing protocol discontinuation • Mild cramping during fluid instillation lasting <30 minutes occurred in 2 patients – One had cramping with DSR so
Slide 10: Change in plasma glucose was modest and transient
Change in plasma glucose was modest and transient 400 300 300 Glucose (mg/dL) Glucose (mg/dL) Glucose (mg/dL) 300 200 200 200 100 100 100 Standard PD solution DSR 0 0 0 0 30 60 90 120 150 180 0 30 60 90 120 150 180 0 30 60 90 120 150 180 Time (minutes) Time (minutes) Time (minutes)
Slide 11: Changes in serum sodium were small
Changes in serum sodium were small 145 145 145 Sodium (mmol/l) Na (mmol/L) 140 Na (mmol/L) 140 Uncorrected 140 135 135 135 serum DSR 130 130 130 sodium Standard PD solution 125 125 125 0 30 60 90 120 150 180 0 30 60 90 120 150 180 0 30 60 90 120 150 180 Time (min) Time (min) Time (minutes) 145 145 1
Slide 12: Secondary efficacy endpoint: Sodium removal was substantially greater with DSR
Secondary efficacy endpoint: Sodium removal was substantially greater with DSR DSR 5 Standard PD solution 4 Sodium (g) 3 2 1 0 0 30 60 90 120 Time (minutes)
Slide 13: Conclusion
Conclusion • These data provide proof of concept that Direct Sodium Removal with a sodium free peritoneal solution is feasible in humans • Safety/tolerability: – Well tolerated – Minimal off target solute removal – Did not result in significant electrolyte disturbances or prolonged or severe hypergl
Slide 14: Future directions
Future directions • Next planned study is a multidose chronic HF study using the alfapump® (Sequana Medical) – Fully implanted system – Developed for refractory ascites – Pump already derisked in this population • Over 700 systems implanted and 400 patient years experience to date Subcutaneous 1 alf