Hydroxychloroquine and Phlebotomy for Treating Porphyria Cutanea Tarda
Condition: Porphyria Cutanea Tarda
MeSH terms: Porphyria Cutanea Tarda; Porphyrias, Hepatic; Porphyria, Erythropoietic; Porphyrias
Study type: Interventional
Phase: Phase 2

Summary: 
      Porphyria cutanea tarda (PCT) is an iron-related disorder that responds to treatment by
      phlebotomy or low-dose hydroxychloroquine, but comparative data on these treatments are
      limited. The hypothesis is that hydroxychloroquine is noninferior to phlebotomy in terms of
      time to remission. Patients with well documented PCT are assigned to treatment by
      randomization if specific criteria are met. All patients are followed until remission -
      defined as achieving a normal plasma porphyrin concentration.
    

Detailed description: 
      Study Design: Pragmatic Interventional study

      Primary Study Objective: To determine and compare time to remission with treatment with
      low-dose hydroxychloroquine or repeated phlebotomy in participants with PCT.

      Secondary Study Objective(s):

        1. To assess the effects of susceptibility factors on responses to treatment of PCT by
           these methods.

        2. To determine and compare rates of recurrence of PCT after treatment with low-dose
           hydroxychloroquine or phlebotomy.

      Study Population and Main Eligibility/ Exclusion Criteria:

      Treatment:

      Hydroxychloroquine 100 mg twice weekly for up to 24 months by mouth vs. phlebotomy 450 mL
      biweekly until target serum ferritin reached, or up to 24 months.

      Safety Issues- 1. Side effects of phlebotomy or hydroxychloroquine, which are the same as in
      clinical practice.

      Primary Outcome Measures:

        1. Time to achievement of a normal plasma total porphyrin level.

        2. Tolerability and safety of both treatments

      Secondary Outcome Measures:

      1. Time to 50% reduction in plasma porphyrin levels. 2. Time to 75% reduction in plasma
      porphyrin levels. 3. Time to normal urinary porphyrin levels

        1. Time to disappearance of a plasma fluorescence peak at neutral pH.

        2. Time to normalization of urinary total porphyrins.

        3. Time to normalization of the urinary total porphyrin pattern by HPLC

        4. Effects of susceptibility factors such as hepatitis C, inherited UROD deficiency, etc.
           on efficacy and safety of the two treatment methods.

        5. Rates of recurrence after each type of treatment and the effects of susceptibility
           factors on recurrence rates.

      Statistical Considerations (sample size and analysis plan): Time to achieving biochemical
      endpoints will be determined from individual subject data. Outcome measures such as time to
      remission will be compared using Cox proportional models to study the effects of
      susceptibility factors on the hazard ratio to compare the two treatments. Additional modeling
      will assess factors affecting the frequency of recurrence and seasonality effects using
      logistic regression modeling and log-rank testing, respectively.

      Sponsors: National Institutes of Health (NIH)
    

Intervention name(s): Hydroxychloroquine; Phlebotomy
Intervention type(s): Drug; Procedure
Intervention description(s): 100 mg by mouth twice weekly; 450 mL every 2 weeks
Other intervention name(s): Plaquenil
Intervention MeSH terms: Hydroxychloroquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Porphyria, rare disease, orphan disease, iron metabolism