Porphyria Cutanea Tarda
Conditions
Keywords
Porphyria, rare disease, orphan disease, iron metabolism
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)
Interventions
DRUGHydroxychloroquine
100 mg by mouth twice weekly
PROCEDUREPhlebotomy
450 mL every 2 weeks
Sponsors
The University of Texas Medical Branch, Galveston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission | To end of study, an average of 3 years | Time to a decrease in plasma porphyrin concentration to less than 0.9 mcg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 50% Reduction in Plasma Porphyrin Level | To end of study, an average of 3 years | 50% reduction in plasma porphyrin level during treatment |
| 75% Reduction in Plasma Porphyrin Level | To end of study, an average of 3 years | Time to 75% reduction in plasma porphyrin level during treatment |
| Number of Days With Normal Urinary Porphyrin Levels | To end of study, an average of 3 years | 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. |
Countries
United States
Participant flow
Recruitment details
Medical clinics and clinical research center
Pre-assignment details
Diagnosis of porphyria cutanea tarda established before enrollment
Participants by arm
| Arm | Count |
|---|---|
| Hydroxychloroquine Low-dose hydroxychloroquine 100 mg by mouth twice weekly
Hydroxychloroquine: 100 mg by mouth twice weekly | 13 |
| Phlebotomy Phlebotomy 450 mL biweekly
Phlebotomy: 450 mL every 2 weeks | 17 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Noncompliance or remission not achieved | 3 | 15 |
Baseline characteristics
| Characteristic | Hydroxychloroquine | Phlebotomy | Total |
|---|---|---|---|
| Age, Continuous | 50.3 years STANDARD_DEVIATION 6 | 51.3 years STANDARD_DEVIATION 5 | 50.9 years STANDARD_DEVIATION 5.4 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 8 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 15 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 13 | 0 / 17 |
| other Total, other adverse events | 3 / 13 | 0 / 17 |
| serious Total, serious adverse events | 4 / 13 | 0 / 17 |
Outcome results
Primary
Remission
Time to a decrease in plasma porphyrin concentration to less than 0.9 mcg/dL
Time frame: To end of study, an average of 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydroxychloroquine | Remission | 6.1 months |
| Phlebotomy | Remission | 6.9 months |
Secondary
50% Reduction in Plasma Porphyrin Level
50% reduction in plasma porphyrin level during treatment
Time frame: To end of study, an average of 3 years
Population: Participants missed some study visits.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydroxychloroquine | 50% Reduction in Plasma Porphyrin Level | 44 days |
| Phlebotomy | 50% Reduction in Plasma Porphyrin Level | 65 days |
Secondary
75% Reduction in Plasma Porphyrin Level
Time to 75% reduction in plasma porphyrin level during treatment
Time frame: To end of study, an average of 3 years
Population: Participants missed some study visits.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydroxychloroquine | 75% Reduction in Plasma Porphyrin Level | 73 days |
| Phlebotomy | 75% Reduction in Plasma Porphyrin Level | 44 days |
Secondary
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.
Time frame: To end of study, an average of 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hydroxychloroquine | Number of Days With Normal Urinary Porphyrin Levels | 175 days |
| Phlebotomy | Number of Days With Normal Urinary Porphyrin Levels | 265 days |