Stopping Hydroxychloroquine for Lupus
(SHIELD Trial)
Recruiting in Palo Alto (17 mi)
+9 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: NYU Langone Health
Must be taking: Hydroxychloroquine
Must not be taking: Immunosuppressants, Biological agents
Disqualifiers: Retinopathy, Dementia, Cognitive impairment, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing if older lupus patients can safely stop taking Hydroxychloroquine, a drug that reduces lupus symptoms but can harm the eyes over time. The study focuses on patients aged 60 and above who have stable disease. Researchers will monitor these patients for an extended period to see if their condition remains stable without the drug.
Do I need to stop my current medications for this trial?
The trial specifically focuses on stopping hydroxychloroquine (HCQ) for lupus patients. Participants must not be on any immunosuppressive drugs or biological agents, and they should have a stable disease status without moderate or severe flares in the past year.
What data supports the effectiveness of the drug hydroxychloroquine for lupus?
Research indicates that hydroxychloroquine helps prevent disease flares (sudden worsening of symptoms) and reduces damage in patients with lupus. It is also associated with improved survival rates and is recommended for all lupus patients due to its efficacy and safety.
12345Is hydroxychloroquine generally safe for humans?
Hydroxychloroquine is generally well-tolerated, but it can cause serious side effects like retinal toxicity (eye damage) and cardiotoxicity (heart damage). Common side effects include skin rashes, stomach issues, and headaches, so regular monitoring by a doctor is important.
678910How does the drug hydroxychloroquine differ from other treatments for lupus?
Hydroxychloroquine is unique because it not only helps manage lupus symptoms like joint pain and skin rashes but also reduces the risk of heart disease by lowering cholesterol and preventing blood clots. It is often used as a long-term treatment to prevent lupus flares and reduce the need for steroids, which can have more severe side effects.
4591112Eligibility Criteria
This trial is for stable/quiescent elderly patients (60+ years) with systemic lupus erythematosus who've been on Hydroxychloroquine (≥200mg daily) for at least 7 years. They must have no recent severe flares, be able to take oral meds, and show no retinal damage. Those on high-dose steroids or immunosuppressants are excluded.Inclusion Criteria
I am 60 years old or older.
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
+4 more
Exclusion Criteria
My disease has not stabilized according to DORIS.
My HCQ level is below 100 ng/ml, indicating I haven't been relying on it.
Ophthalmologic evidence of retinopathy
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive either Hydroxychloroquine or a matching placebo every 2 months for one year to assess disease activity and flares
12 months
6 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests the safety of stopping Hydroxychloroquine in older adults with inactive lupus by comparing it against a placebo. Participants will be randomly assigned to either continue HCQ or switch to a placebo and monitored bi-monthly for a year to track disease activity.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Hydroxychloroquine (HCQ)Experimental Treatment1 Intervention
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.
Group II: HCQ-Matching PlaceboPlacebo Group1 Intervention
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 is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Plaquenil for:
- Malaria
- Rheumatoid Arthritis
- Systemic Lupus Erythematosus
🇪🇺 Approved in European Union as Plaquenil for:
- Malaria
- Rheumatoid Arthritis
- Systemic Lupus Erythematosus
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Penn State MS Hershey Medical CenterHershey, PA
Hackensack Meridian HealthHackensack, NJ
VA NY Harbor Healthcare SystemNew York, NY
NYC Health + Hospitals/BellevueNew York, NY
More Trial Locations
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Who Is Running the Clinical Trial?
NYU Langone HealthLead Sponsor
National Institutes of Health (NIH)Collaborator
References
A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. [2022]The antimalarial drug hydroxychloroquine is thought to be effective in controlling some of the manifestations of systemic lupus erythematosus, but its effectiveness has not been demonstrated conclusively.
Why lupus patients discontinue antimalarials in real life: A 50 years-experience from a reference centre. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Because of the efficacy and good safety profile of antimalarials in systemic lupus erythematosus (SLE), hydroxychloroquine (HCQ) is currently recommended in all SLE patients. However, patients' compliance was reported as suboptimal. This study aims to elucidate the reasons for discontinuing antimalarials in a large series of SLE patients followed in a single centre during the last 50 years.
Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). [2022]In patients with systemic lupus erythematosus (SLE), hydroxychloroquine prevents disease flares and damage accrual and facilitates the response to mycophenolate mofetil in those with renal involvement. A study was undertaken to determine whether hydroxychloroquine also exerts a protective effect on survival.
Outcomes of Systemic Lupus Erythematosus in Patients who Discontinue Hydroxychloroquine. [2022]Hydroxychloroquine (HCQ) is an antimalarial drug that is recommended as a safe, daily prophylactic intervention for individuals with systemic lupus erythematosus (SLE) based on previous studies that showed an association of HCQ use with reductions in flares compared with placebo. Our study aims to determine whether the discontinuation of HCQ leads to relapse of disease and whether the duration of HCQ use impacts the success of its eventual discontinuation.
Discontinuation of antimalarial drugs in systemic lupus erythematosus. [2013]To assess the reasons for and timing of discontinuation of antimalarial drugs, principally hydroxychloroquine (HCQ), in systemic lupus erythematosus (SLE).
Retinal toxicity secondary to Plaquenil therapy. [2016]Hydroxychloroquine sulfate (Plaquenil; Sanofi-Aventis, Bridgewater, New Jersey) is an antimalarial agent, which is sometimes used for the treatment of certain autoimmune disorders. Its use has been associated with ocular side effects; the most concerning is toxic maculopathy.
Hydroxychloroquine in nephrology: current status and future directions. [2023]Hydroxychloroquine is one of the oldest disease-modifying anti-rheumatic drugs in clinical use. The drug interferes with lysosomal activity and antigen presentation, inhibits autophagy, and decreases transcription of pro-inflammatory cytokines. Owing to its immunomodulatory, anti-inflammatory, anti-thrombotic effect, hydroxychloroquine has been an integral part of therapy for systemic lupus erythematosus and lupus nephritis for several decades. The therapeutic versatility of hydroxychloroquine has led to repurposing it for other clinical conditions, with recent studies showing reduction in proteinuria in IgA nephropathy. Research is also underway to investigate the efficacy of hydroxychloroquine in primary membranous nephropathy, Alport's syndrome, systemic vasculitis, anti-GBM disease, acute kidney injury and for cardiovascular risk reduction in chronic kidney disease. Hydroxychloroquine is well-tolerated, inexpensive, and widely available and therefore, should its indications expand in the future, it would certainly be welcomed. However, clinicians should be aware of the risk of irreversible and progressive retinal toxicity and rarely, cardiomyopathy. Monitoring hydroxychloroquine levels in blood appears to be a promising tool to evaluate compliance, individualize the dose and reduce the risk of retinal toxicity, although this is not yet standard clinical practice. In this review, we discuss the existing knowledge regarding the mechanism of action of hydroxychloroquine, its utility in lupus nephritis and other kidney diseases, the main adverse effects and the evidence gaps that need to be addressed in future research. Created with Biorender.com. HCQ, hydroxychloroquine; GBM, glomerular basement membrane; mDC, myeloid dendritic cell; MHC, major histocompatibility complex; TLR, toll-like receptor.
Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. [2022]Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects.
[Current view on chloroquine derivative treatment from rheumatologist perspective and possible ocular side effects]. [2016]Anti-malarial drugs specifically hydroxychloroquine (HCQ) or chloroquine (CQ) are very effective in treating and preventing the symptoms of systemic lupus erythematosus and other connective tissue diseases. These medications have shown to improve joint and muscle pain and arthritis, skin rashes, fatique, fever and also to control systemic signs of lupus as pericarditis or pleuritis. Shortterm and long-term treatment reduce cholesterol and have anti-platelet effect with decreasing risk of cardiovascular disease. The lupus patients on anti-malarials have also lower risk of cumulative organ damage due to reduce the amount of steroids. They may help to decrease lupus flares, mortality and are the key to controlling lupus long term outcome. Some lupus patients should be on anti-malarials for the rest of their life. For this reason, the key question is weather these drugs are absolutely safe and can be long term used in all lupus patients as a background therapy? Potential non-specific side effects occur very rare and are usually minor and last for short period. The major concerns are retinal deposits damage which could be potential reversible especially during hydroxychloroquine treatment. Nevertheless, ophthalmologist examination is still needed before starting to take HCQ or CQ and at to follow-up visits every 6-12 months. In conclusion it seems that anti-malarials are safe and have more clinical benefits than risks and from rheumatologist point of view should be more widely use in all lupus patients.
The safety profile of hydroxychloroquine: major cutaneous and extracutaneous adverse events. [2022]Hydroxychloroquine is an established therapy for several rheumatological disorders, and very recently it has been proposed as a possible treatment for the new coronavirus disease 2019 even if recent randomised trials did not prove any benefit. Notably, hydroxychloroquine has been associated with a heterogeneous range of cutaneous and extra-cutaneous adverse events. We carried out a narrative review of the literature up to November 1st, 2020, related to the safety of hydroxychloroquine. In particular, cutaneous and extra-cutaneous adverse events associated with hydroxychloroquine were reviewed. The following databases were consulted: PubMed, Embase, Google Scholar and ResearchGate. The research of articles was conducted by using the following search terms: ''hydroxychloroquine," ''adverse event/effect,'' "cutaneous", "skin", "cardiotoxicity", "retinopathy", gastrointestinal and neurological toxicity". The main indication for which hydroxychloroquine was used in the reports was an immune mediated disorder. Adverse events were described mostly in females over 50 years of age. The most common cutaneous adverse effect was maculopapular and erythematous rash occurring within 4 weeks of initiating hydroxychloroquine and disappearing within few weeks of discontinuation. Gastrointestinal symptoms and headache were the most frequent extracutaneous manifestations. Rarer cutaneous manifestations include hyperpigmentation, psoriasiform dermatitis, photodermatitis, stomatitis, melanonychia and hair loss. More severe conditions were acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis, and among extra-cutaneous adverse events cardiotoxicity and retinopathy. Since hydroxychloroquine is widely prescribed in rheumatology, it is important for rheumatologists to be familiar with its safety profile.
Antimalarial drugs in systemic lupus erythematosus: use in pregnancy. [2019]The 4-aminoquinoline radical containing antimalarial drugs are also used in the management of various connective tissue diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis. These agents are particularly useful for the management of inflammatory polyarthritis and skin disease. By raising the pH in intracellular compartments, these drugs interfere with normal phagocytic function which consequently enables them to interfere with antigen processing. Other actions include inhibition of platelet aggregation, this is advantageous in patients with phospholipid antibodies (aPL) which are known to predispose patients to recurrent arterial and venous clinical thrombotic events. Hydroxychloroquine has also been demonstrated to reduce serum lipid levels including cholesterol, triglycerides and low density lipoproteins. As it is now known that patients with SLE are at risk for accelerated artherogenesis and premature heart disease, this action may be an added benefit for these patients. The use of the 4-aminoquinoline radical containing antimalarial drugs during pregnancy is controversial. It is known that these agents can cross the placenta and are deposited in fetal pigmented tissues. These findings have led to the recommendation that these agents should be discontinued in pregnancy for patients with connective tissue diseases even though they have long been recommended for malarial prophylaxis in pregnant women travelling to malarial infested areas. Flares of SLE disease have been documented when these agents are discontinued and as flares of SLE disease activity are known to be detrimental to pregnancy outcome in patients with SLE, it is our opinion that these drugs should not be discontinued during pregnancy in a patient with lupus, particularly when the known terminal elimination half life is 1 to 2 months.
Treatment of lupus skin involvement with quinacrine and hydroxychloroquine. [2013]To evaluate the efficacy of hydroxychloroquine (HCQ) and quinacrine (Qn) association, at two different dosages, in treatment of lupus skin lesions not responding to HCQ alone. Thirty-four patients, affected by cutaneous and systemic lupus erythematosus, were retrospectively analysed. They were treated by HCQ (5 mg/Kg/qd) and Qn with two regimens: 100 mg/qd (29 cases) and 50 mg/qd (5 cases). Discoid lupus erythematosus (19 cases), acute malar rash (6 cases), chilblain lupus (4 cases) showed a significant improvement with combination therapy (P = 0.009, P = 0.019, and P = 0.04, respectively). Ten patients with subacute cutaneous lupus showed a partial response, whereas lupus profundus didn't improve. The same overall response rate was recorded comparing two Qn regimens, but subjects taking 100 mg/qd improved more rapidly than the others (P = 0.001). Ten patients developed side effects, mainly represented by skin yellowish discolouration. Depression and severe headache with nausea, which were globally recorded in two cases, led to drug withdrawal. One additional case of hepatitis was recorded in a patient with preexisting Hepatitis C virus (HCV) infection. Combination of HCQ and Qn is rapidly effective at 100 mg/qd and well tolerated in the treatment of lupus skin lesions unresponsive to HCQ alone.