Hydroxychloroquine and Phlebotomy for Treating Porphyria Cutanea Tarda

The University of Texas System (UT)

Status and phase: Completed; Phase 2

Conditions: Porphyria Cutanea Tarda

Treatments: Procedure: Phlebotomy; Drug: Hydroxychloroquine

Study type: Interventional

Funder types: Other

Identifiers

NCT01573754

R01FD002604

FDA-2604

Details and patient eligibility

About

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.

Full 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

2. Time to disappearance of a plasma fluorescence peak at neutral pH.

3. Time to normalization of urinary total porphyrins.

4. Time to normalization of the urinary total porphyrin pattern by HPLC

5. Effects of susceptibility factors such as hepatitis C, inherited UROD deficiency, etc. on efficacy and safety of the two treatment methods.

6. 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)

Enrollment: 48 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 2 patient groups

Hydroxychloroquine

Experimental group

Description:

Low-dose hydroxychloroquine 100 mg by mouth twice weekly

Treatment:

Drug: Hydroxychloroquine

Phlebotomy

Active Comparator group

Description:

Phlebotomy 450 mL biweekly

Treatment:

Procedure: Phlebotomy