Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease
- Conditions
- Systemic Lupus Erythematosus
- Interventions
- Drug: Placebo
- Registration Number
- NCT05799378
- Lead Sponsor
- NYU Langone Health
- Brief Summary
Hydroxychloroquine (HCQ) is a systemic lupus erythematosus (SLE) medication that has been very effective in reducing lupus disease activity and keeping patients stable with reduced symptoms. Despite a track record of safety with regard to infection compared to traditional immunosuppressive agents, the risk of HCQ retinal toxicity escalates with continued use. Evaluation using sensitive standard of care approaches suggests nearly a third of patients accrue retinal damage. Data are needed to accurately weigh the balance between accumulating ocular exposure of HCQ versus the risk of disease flare in a population that may have more inactive disease than younger patients. The purpose of this trial is to address the safety of withdrawal of HCQ in SLE patients =60 years old. The central hypothesis is that HCQ can be safely discontinued in stable/quiescent patients assessed by validated disease activity and flare instruments in the context of serologic, cytokine and transcriptomic profiling. Patients will be randomized to either the placebo or active arm and followed every 2 months for one year to assess disease activity and flares.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 330
-
Provision of signed and dated informed consent form
-
Stated willingness to comply with all study procedures and availability for the duration of the study
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Age ≥ 60 years at time of enrollment
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Normal OCT and VF assessment within 6 months of screening visit
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Ability to take oral medication
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Have established SLE (≥ 4 ACR criteria or SLICC criteria or ≥ 10 points by EULAR criteria, SLE diagnosed at least seven years ago)
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Stable disease at screening visit by attaining DORIS remission (meeting all criterion listed below) and not on any immunosuppressants.
- Criterion 1: Clinical SLEDAI= 0
- Criterion 2: SELENA-SLEDAI PGA ≤ 0.5 (on a scale from 0-3, where 0 is no disease activity and 3 is maximum disease activity)
- Criterion 3: Current prednisolone (or equivalent corticosteroid) dose ≤ 5 mg daily
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No moderate or severe flares one year prior to screening
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Taking ≥ 200 HCQ daily for ≥ 7 years
- Any patient that does not attain stable disease status by DORIS
- Ophthalmologic evidence of retinopathy (these patients would be advised to discontinue HCQ and therefore unethical to randomize for this study)
- Clinical SLEDAI > 0
- Taking > 5 mg/day prednisone
- Taking any immunosuppressive drugs or biological agents (including: methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide, cyclosporine, cyclophosphamide, tacrolimus, rituximab, and belimumab)
- Any reason the treating rheumatologist is concerned about ongoing activity not captured by SLEDAI
- HCQ level < 100 ng/ml as this would support noncompliance and less reliance on HCQ to control activity
- Patient unwilling or unable to comply with study procedures for any reason
- Any indications of potentially diminished capacity, such as a diagnosis of dementia or cognitive impairment (including, but not limited to stroke-related cognitive impairment)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HCQ-Matching Placebo Placebo Patients will receive a 90-day supply of HCQ-matching placebo at their screening visit, at 2 months, 4 months, 6 months, 8 months, and 10 months. All patients will return their current supply along with a completed dosing diary at each visit and receive a new supply in exchange. The HCQ-matching placebo dose administered will match each patient's dosage of HCQ at enrollment. Hydroxychloroquine (HCQ) Hydroxychloroquine Patients will receive a 90-day supply of HCQ at their screening visit, at 2 months, 4 months, 6 months, 8 months, and 10 months. All patients will return their current supply along with a completed dosing diary at each visit and receive a new supply in exchange. The HCQ dose administered will match each patient's dosage of HCQ at enrollment.
- Primary Outcome Measures
Name Time Method Number of Participants who Develop Moderate or Severe Flare based on the Revised SELENA SLEDAI Flare Index (rSFI) Up to Month 12 Number of participants who experience moderate or severe flares as defined by the rSFI.
- Secondary Outcome Measures
Name Time Method Number of Participants with New-Onset Diabetes Up to Month 12 Number of Participants with New Retinal Toxicity Up to Month 12 Number of Participants who Begin Prednisone Treatment Up to Month 12 Number of Participants who Increase Prednisone Use Up to Month 12 Number of Participants who Experience Thromboembolic Event Up to Month 12 Thromboembolic event includes, but is not limited to, venous thrombosis.
Change in 36-Item Short Form Survey Instrument (SF-36) Score Baseline, Month 12 The SF-36 is 36-item self-rated measure of quality of life. A scoring algorithm is used to convert the raw scores into a range from zero (the respondent has the worst possible health) to 100 where the respondent is in the best possible health.
Physician Global Assessment (PGA) Score at Month 12 Month 12 The Physician Global Assessment (PGA) of treatment response measures the overall response to treatment as assessed by the physician. The score ranges from +4 to (-4), where 4 = Markedly Improved, 0 = No change, and (-4) = markedly worse.
Number of Participants who Develop Moderate Flare based on rSFI Up to Month 12 Number of participants who experience moderate flares as defined by the rSFI.
Number of Participants who Experience Cardiovascular Event Up to Month 12 Change in 29-Question Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score Baseline, Month 12 PROMIS-29 consists of 29 questions rated on a scale from 1-5. The raw score is converted to a final T-score metric with a mean T-score of 50 and a standard deviation of 10. The final score ranges from 0 (worst possible outcome) to 100 (best possible outcome). The questionnaire assesses seven domains - depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities.
Trial Locations
- Locations (10)
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Montefiore Medical Center/Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
VA NY Harbor Healthcare System
🇺🇸New York, New York, United States
NYC Health + Hospitals/Bellevue
🇺🇸New York, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
Oklahoma Medical Research Foundation
🇺🇸Oklahoma City, Oklahoma, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Columbia University Irving Medical Center/New York Presbyterian
🇺🇸New York, New York, United States
Hackensack Meridian Health
🇺🇸Hackensack, New Jersey, United States
Penn State MS Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States