search
Back to results

Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease (SHIELD)

Primary Purpose

Systemic Lupus Erythematosus

Status
Not yet recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Hydroxychloroquine
Placebo
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring Hydroxychloroquine, systemic lupus erythematosus, elderly lupus disease, lupus, sle, plaquenil

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Age ≥ 60 years at time of enrollment Normal OCT and VF assessment within 6 months of screening visit Ability to take oral medication Have established SLE (≥ 4 ACR criteria or SLICC criteria or ≥ 10 points by EULAR criteria, SLE diagnosed at least seven years ago) 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 No moderate or severe flares one year prior to screening Taking ≥ 200 HCQ daily for ≥ 7 years Exclusion Criteria: 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)

Sites / Locations

  • University of California, Los Angeles
  • Hackensack Meridian Health
  • Montefiore Medical Center/Albert Einstein College of Medicine
  • VA NY Harbor Healthcare System
  • NYC Health + Hospitals/Bellevue
  • NYU Langone Health
  • Hospital for Special Surgery
  • Columbia University Irving Medical Center/New York Presbyterian
  • Oklahoma Medical Research Foundation
  • Penn State MS Hershey Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Hydroxychloroquine (HCQ)

HCQ-Matching Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants who Develop Moderate or Severe Flare based on the Revised SELENA SLEDAI Flare Index (rSFI)
Number of participants who experience moderate or severe flares as defined by the rSFI.

Secondary Outcome Measures

Number of Participants who Develop Moderate Flare based on rSFI
Number of participants who experience moderate flares as defined by the rSFI.
Physician Global Assessment (PGA) Score at 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 Begin Prednisone Treatment
Number of Participants who Increase Prednisone Use
Number of Participants who Experience Thromboembolic Event
Thromboembolic event includes, but is not limited to, venous thrombosis.
Number of Participants who Experience Cardiovascular Event
Number of Participants with New-Onset Diabetes
Number of Participants with New Retinal Toxicity
Change in 36-Item Short Form Survey Instrument (SF-36) Score
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.
Change in 29-Question Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score
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.

Full Information

First Posted
March 23, 2023
Last Updated
July 13, 2023
Sponsor
NYU Langone Health
Collaborators
National Institutes of Health (NIH)
search

1. Study Identification

Unique Protocol Identification Number
NCT05799378
Brief Title
Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease
Acronym
SHIELD
Official Title
A Phase III, Randomized, Double-Blind Placebo-Controlled, Non-Inferiority, Multi-Center Study of the Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
June 30, 2027 (Anticipated)
Study Completion Date
December 21, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
Keywords
Hydroxychloroquine, systemic lupus erythematosus, elderly lupus disease, lupus, sle, plaquenil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
330 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine (HCQ)
Arm Type
Experimental
Arm Description
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.
Arm Title
HCQ-Matching Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Hydroxychloroquine 200mg capsules. Administered orally.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Hydroxychloroquine-matching placebo capsule. Administered orally.
Primary Outcome Measure Information:
Title
Number of Participants who Develop Moderate or Severe Flare based on the Revised SELENA SLEDAI Flare Index (rSFI)
Description
Number of participants who experience moderate or severe flares as defined by the rSFI.
Time Frame
Up to Month 12
Secondary Outcome Measure Information:
Title
Number of Participants who Develop Moderate Flare based on rSFI
Description
Number of participants who experience moderate flares as defined by the rSFI.
Time Frame
Up to Month 12
Title
Physician Global Assessment (PGA) Score at Month 12
Description
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.
Time Frame
Month 12
Title
Number of Participants who Begin Prednisone Treatment
Time Frame
Up to Month 12
Title
Number of Participants who Increase Prednisone Use
Time Frame
Up to Month 12
Title
Number of Participants who Experience Thromboembolic Event
Description
Thromboembolic event includes, but is not limited to, venous thrombosis.
Time Frame
Up to Month 12
Title
Number of Participants who Experience Cardiovascular Event
Time Frame
Up to Month 12
Title
Number of Participants with New-Onset Diabetes
Time Frame
Up to Month 12
Title
Number of Participants with New Retinal Toxicity
Time Frame
Up to Month 12
Title
Change in 36-Item Short Form Survey Instrument (SF-36) Score
Description
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.
Time Frame
Baseline, Month 12
Title
Change in 29-Question Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score
Description
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.
Time Frame
Baseline, Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Age ≥ 60 years at time of enrollment Normal OCT and VF assessment within 6 months of screening visit Ability to take oral medication Have established SLE (≥ 4 ACR criteria or SLICC criteria or ≥ 10 points by EULAR criteria, SLE diagnosed at least seven years ago) 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 No moderate or severe flares one year prior to screening Taking ≥ 200 HCQ daily for ≥ 7 years Exclusion Criteria: 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mala Masson
Phone
(212) 263-0372
Email
Mala.Masson@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Izmirly
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jill Buyon
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Hackensack Meridian Health
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Montefiore Medical Center/Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
VA NY Harbor Healthcare System
City
New York
State/Province
New York
ZIP/Postal Code
10010
Country
United States
Facility Name
NYC Health + Hospitals/Bellevue
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Columbia University Irving Medical Center/New York Presbyterian
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Oklahoma Medical Research Foundation
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Penn State MS Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The de-identified participant data from the final research dataset used in the published manuscript will be shared with investigators whose proposed use of the data has been approved by the co-PIs, Dr. Peter M. Izmirly and Dr. Jill P. Buyon, beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Peter.Izmirly@nyulangone.org and Jill.Buyon@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research. A copy of an informed consent form will also be made available.
IPD Sharing Time Frame
Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
IPD Sharing Access Criteria
Investigators whose proposed use of the data has been approved by co-PIs, Dr. Peter M. Izmirly and Dr. Jill P. Buyon, will be granted access to the data to achieve aims outlined in the approved proposal. Requests should be directed to Peter.Izmirly@nyulangone.org and Jill.Buyon@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Learn more about this trial

Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

We'll reach out to this number within 24 hrs