Hydroxychloroquine and Phlebotomy for Treating Porphyria Cutanea Tarda

Study Overview
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Brief Summary
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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
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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): To assess the effects of susceptibility factors on responses to treatment of PCT by these methods. 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: Time to achievement of a normal plasma total porphyrin level. 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 Time to disappearance of a plasma fluorescence peak at neutral pH. Time to normalization of urinary total porphyrins. Time to normalization of the urinary total porphyrin pattern by HPLC Effects of susceptibility factors such as hepatitis C, inherited UROD deficiency, etc. on efficacy and safety of the two treatment methods. 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)

Official Title
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A Prospective Comparison of Low Dose Hydroxychloroquine and Phlebotomy in the Treatment of Porphyria Cutanea Tarda. IRB 02-435

Conditions
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Porphyria Cutanea Tarda

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Procedure: Phlebotomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented porphyria cutanea tarda (PCT) Willing to give informed consent Age 18 or greater Exclusion Criteria: Blistering skin lesions due to another condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br>Low-dose hydroxychloroquine 100 mg by mouth twice weekly | Drug: Hydroxychloroquine<br>* 100 mg by mouth twice weekly<br>* Other names: Plaquenil;|
| Active Comparator: Phlebotomy<br>Phlebotomy 450 mL biweekly | Procedure: Phlebotomy<br>* 450 mL every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission | Time to a decrease in plasma porphyrin concentration to less than 0.9 mcg/dL | To end of study, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 50% Reduction in Plasma Porphyrin Level | 50% reduction in plasma porphyrin level during treatment | To end of study, an average of 3 years | 
| 75% Reduction in Plasma Porphyrin Level | Time to 75% reduction in plasma porphyrin level during treatment | To end of study, an average of 3 years | 
| Number of Days With Normal Urinary Porphyrin Levels | Number of days to normal urinary porphyrin levels for participants treated for Porphyria Cutanea Tarda (PCT). Days are summed together for all participants for a single value in each Arm. | To end of study, an average of 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Porphyria, rare disease, orphan disease, iron metabolism