Hydroxychloroquine and Phlebotomy for Treating Porphyria Cutanea Tarda

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

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.

Study Overview

• Status: Completed
• Conditions: Porphyria Cutanea Tarda
• Intervention / Treatment: Drug: Hydroxychloroquine; Procedure: Phlebotomy

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)

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston

Publications and helpful links

General Publications

• Singal AK, Kormos-Hallberg C, Lee C, Sadagoparamanujam VM, Grady JJ, Freeman DH Jr, Anderson KE. Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Clin Gastroenterol Hepatol. 2012 Dec;10(12):1402-9. doi: 10.1016/j.cgh.2012.08.038. Epub 2012 Sep 14.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2006
• Primary Completion (Actual): July 6, 2021
• Study Completion (Actual): July 6, 2021

Study Registration Dates

• First Submitted: April 5, 2012
• First Submitted That Met QC Criteria: April 6, 2012
• First Posted (Estimate): April 9, 2012

Study Record Updates

• Last Update Posted (Actual): February 17, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Porphyria, rare disease, orphan disease, iron metabolism
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Skin Diseases; Liver Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Porphyria Cutanea Tarda; Porphyrias, Hepatic; Porphyria, Erythropoietic; Porphyrias; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: FDA-2604; R01FD002604 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Through a NIH data repository at some future time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No