Clinical trial NCT01573754: Hydroxychloroquine and Phlebotomy for Treating Porphyria Cutanea Tarda
Official title: A Prospective Comparison of Low Dose Hydroxychloroquine and Phlebotomy in the Treatment of Porphyria Cutanea Tarda. IRB 02-435
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Porphyria Cutanea Tarda
Keywords: Porphyria, rare disease, orphan disease, iron metabolism
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2012-04-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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

Primary outcomes:
measure: Remission
timeFrame: To end of study, an average of 3 years
Secondary outcomes:
measure: 50% Reduction in Plasma Porphyrin Level
timeFrame: To end of study, an average of 3 years
measure: 75% Reduction in Plasma Porphyrin Level
timeFrame: To end of study, an average of 3 years
measure: Number of Days With Normal Urinary Porphyrin Levels
timeFrame: To end of study, an average of 3 years
Other outcomes:
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: University of Texas
name: Karl E Anderson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.