Hydroxychloroquine and Phlebotomy for Treating Porphyria Cutanea Tarda

NCT ID: NCT01573754

Last Updated: 2023-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-21
• Study Completion Date: 2021-07-06

Brief 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)

Conditions

Porphyria Cutanea Tarda

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hydroxychloroquine

Low-dose hydroxychloroquine 100 mg by mouth twice weekly

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

100 mg by mouth twice weekly

Phlebotomy

Phlebotomy 450 mL biweekly

Group Type: ACTIVE_COMPARATOR

Phlebotomy

Intervention Type: PROCEDURE

450 mL every 2 weeks

Interventions

Hydroxychloroquine

100 mg by mouth twice weekly

Intervention Type: DRUG

Phlebotomy

450 mL every 2 weeks

Intervention Type: PROCEDURE

Other Intervention Names

Plaquenil

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karl E Anderson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Locations

University of Texas Medical Branch

Galveston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 22985607 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

R01FD002604

Identifier Type: FDA

Identifier Source: secondary_id

View Link

FDA-2604

Identifier Type: -

Identifier Source: org_study_id