Author + information
- Howard C. Dittrich,
- Julie Iwashita,
- Jean Chang,
- Scott Thomson,
- Thomas H. Oliphant,
- David Smith,
- Joel M. Neutel,
- Detlef Albrecht and
- F. John Gennari
Because of an inadequate response to diuretics in some heart failure (HF) patients, removal of sodium and fluid via the gastrointestinal (Gl) tract merits consideration. The orally administered, non-absorbed, cross-linked acrylic acid polymer, CLP-1001, has been shown to produce significant weight loss and HF symptom improvement compared to placebo when added to guideline therapy including an aldosterone antagonist (AA). Because aldosterone receptors in the Gl tract modulate cation transport, the influence of AA on CLP-1001's efficacy was examined.
18 ambulatory NYHA Class Ill (15) or edematous Class II (3) HF patients (72% white, 72% males, age 43-86, EF 24-38%) on guideline therapy were enrolled in a crossover trial in a phase 1 unit where CLP-1001 was given with and without AA. Dietary ion content was tightly controlled. All fecal and urinary output was collected and efficacy was based on changes in fecal weight and sodium content. A run-in of 5 days in each treatment period was followed by 7 days of CLP-1001, 15 g daily, with a 7-day washout between treatment periods. Half of the subjects were randomized to AA (spironolactone 25 mg/day) throughout period 1, half throughout period 2 (AA was the crossover variable).
CLP-1001 was well tolerated. Weight loss over the 2 week treatment period was similar when CLP-1001 + AA (−1.81±1.27 [mean±SD] kg) was given vs. CLP-1001 alone (−1.60±1.05 kg). Mean daily fecal weight increase compared to baseline was also similar with (+119.0±107 g) or without AA (+144.7±86.5 g). Likewise, mean daily fecal sodium content increase compared to baseline was not different in the presence (+502.0±342.5 mg) or absence (+635.1±441.1 mg) of AA. No changes were noted in serum sodium. While serum potassium was unchanged (−0.05±0.43 mEq/L) when CLP-1001 was given with AA, it decreased significantly (−0.30±0.44 mEq/L) on CLP-1001 without AA (p=0.0238).
The beneficial effects of CLP-1001 on removal of sodium and fluid by the Gl tract in HF are not influenced by the co-administration of AA, suggesting that the drug may prove effective regardless of the use of AA. However, use of CLP-1001 will call for appropriate monitoring of serum potassium.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Heart Failure: Pharmacologic Therapy
Abstract Category: 17. Heart Failure: Therapy
Presentation Number: 1223-304
- 2013 American College of Cardiology Foundation