DITPA (3,5-diiodothyropropionic acid), a thyroid hormone analog to treat heart failure: Phase II trial veterans affairs cooperative study

BACKGROUND: In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. METHODS AND RESULTS: This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n≤57 to DITPA, n≤29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failurespecific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (-20%), low-density lipoprotein cholesterol (-30%), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. CONCLUSIONS: DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.