Heme Arginate and Tin Mesoporphyrin for Acute Porphyria Treatment and Prevention

PROTOCOL OUTLINE: This project involves 4 studies: an unblinded multicenter treatment study, an unblinded prevention study, a controlled dose-ranging study, and a controlled drug combination dose-ranging study. In the treatment study, participants with acute attacks of porphyria receive intravenous heme arginate daily for 4 days. Treatment may be extended to 7 days in patients with severe attacks and slow recovery; these data are analyzed separately. In the prevention study, participants receive weekly infusions of heme arginate for 6 months. Treatment may be extended in selected cases; these data are analyzed separately. If an acute attack occurs, patients are treated with a standard course of heme arginate. Participants are followed weekly for 6 months after preventive treatment. In the dose-ranging study, 4 groups of 3 patients are randomly assigned to standard and low-dose heme arginate infusions, administered daily for 4 days. After a washout of 4-12 weeks, patients are crossed to a second dose. In 2 of the 4 groups, patients cross between heme arginate and a normal saline control. In the combination dose-ranging study, 4 groups of 3 patients are randomly assigned to 1 of 2 doses of tin mesoporphyrin. After a 4-12 week washout, these patients are crossed to a standard or low-dose heme arginate infusion. After a second 4-12 week washout, patients are given a combination infusion of tin mesoporphyrin followed by heme arginate. All participants are given a special diet to prevent fluctuations in porphyrin precursors.