search
Back to results

Dipyridamole Assessment for Flare Reduction in Systemic Lupus Erythematosus (SLE) (DARE)

Primary Purpose

Systemic Lupus Erythematosus

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
extended release dipyridamole 200mg/aspirin 25mg
81mg aspirin
Sponsored by
Oklahoma Medical Research Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring lupus, dipyridamole

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with SLE meeting the 1997 ACR Classification Criteria
  • Evidence of positive ANA or anti-dsDNA within one year of screening
  • SLEDAI ≥4 or ≥1 BILAG A or B at screening, despite standard of care

Exclusion Criteria:

  • Leukopenia (WBC <2.000/mm3) or lymphopenia (lymphocytes < 300/mm3)
  • AST or ALT >3 times above normal cut off values
  • Acute lupus nephritis defined as class II, IV or V nephritis diagnosed within 6 months or prot/creat > 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis
  • Active CNS lupus affecting mental status
  • Pregnancy or breast feeding
  • Current requirement for anticoagulation
  • Contraindication to aspirin or dipyridamole, including history of recent or severe GI bleeding, hemoglobin <9 mg/dL, platelet count of <30,000 /mm3 or unstable platelet count
  • Any other medical condition, whether or not related to lupus which, in the opinion of the investigator would render the patient inappropriate or too unstable to complete the study protocol
  • Inability or unwillingness to understand and/or sign informed consent

Sites / Locations

  • Oklahoma Medical Research Foundation

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

extended release dipyridamole/aspirin

aspirin

Arm Description

extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks

half a tablet of a 81mg aspirin twice daily for 24 weeks

Outcomes

Primary Outcome Measures

British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
This is a landmark measure of percentage of patients who meet response criteria. To meet the BICLA response measure a patient must, compared to baseline, have a decrease in all moderate or severe scores on the British Isles Lupus Assessment Group (BILAG) index by at least one severity grade (Severe disease (BILAG A score) must drop to at least moderate (B or better) and B must drop to at least mild (C or not present). Also, there must be no increase in any other BILAG organ scores, no increase in The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and no increase in the physician's global assessment (PGA) by more than 10% of the scale. Furthermore, there may no off protocol medication increases. Note on all scales mentioned a higher score signifies greater disease activity. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76.

Secondary Outcome Measures

Systemic Lupus Erythematosus Responder Index (SRI) 4
This is a landmark analysis of percentage of patients who meet the following response criteria: Compared to baseline there must be a 4 point decrease in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), no increase in The British Isles Lupus Assessment Group (BILAG) Index score and no more of an increase in Physician's Global Assessment (PGA) than 10% of the scale. As assessed here, there must also be no off protocol increase in medications. All scales signify worsening disease when scores increase. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76.
SRI Component Analyses: 4 Point Drop in SLEDAI
This is a landmark analysis of percentage of patients who, compared to baseline, have a 4 point drop in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). A 4 point decrease signifies a clinically significant decrease in disease activity as reported in many studies and as commonly used as a clinical endpoint in trials. SLEDAI could range 0-105 but is rarely greater than 20.

Full Information

First Posted
January 2, 2013
Last Updated
November 3, 2020
Sponsor
Oklahoma Medical Research Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT01781611
Brief Title
Dipyridamole Assessment for Flare Reduction in Systemic Lupus Erythematosus (SLE)
Acronym
DARE
Official Title
Dipyridamole Assessment for Flare Reduction in SLE
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Why Stopped
Slow recruitment
Study Start Date
February 2013 (Actual)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oklahoma Medical Research Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Dipyridamole, a medication extensively used in combination with aspirin for stroke prevention, is a promising new treatment for lupus. Dipyridamole has been shown to inhibit certain lymphocyte populations that are over-reactive in lupus and to delay the emergence of lupus-related pathology in mice with lupus. The investigators are interested in investigating the efficacy of dipyridamole in preventing flares in patients with lupus and its impact on biomarkers of disease activity.
Detailed Description
T cells in systemic lupus erythematosus (SLE) express an abnormal phenotype characterized by increased effector functions and deficient regulatory responses. Dipyridamole, a phosphodiesterase inhibitor extensively used in combination with low dose aspirin in secondary stroke prevention, has been proposed as a specific T cell directed treatment for SLE. Dipyridamole inhibits the calcium/calcineurin/NF-AT pathway in SLE T cells in vitro and abrogates expression of cytokines and costimulatory molecules, eventually also affecting B cell responses. Dipyridamole delays the emergence of lupus related pathology in lupus prone mice, but has not yet been studied in humans with SLE. The investigators aim to investigate the efficacy of dipyridamole in the prevention of flares in SLE patients after withdrawal of background immunosuppressive medications. The investigators will additionally evaluate the safety and tolerability of dipyridamole and its impact on quality of life measures in this population. Furthermore, the effect of dipyridamole on T and B cell biomarkers will be examined.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
Keywords
lupus, dipyridamole

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Pilot study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
extended release dipyridamole/aspirin
Arm Type
Experimental
Arm Description
extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks
Arm Title
aspirin
Arm Type
Active Comparator
Arm Description
half a tablet of a 81mg aspirin twice daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
extended release dipyridamole 200mg/aspirin 25mg
Other Intervention Name(s)
Aggrenox
Intervention Description
one tablet twice daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
81mg aspirin
Other Intervention Name(s)
ASA
Intervention Description
half a tablet twice daily for 24 weeks
Primary Outcome Measure Information:
Title
British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
Description
This is a landmark measure of percentage of patients who meet response criteria. To meet the BICLA response measure a patient must, compared to baseline, have a decrease in all moderate or severe scores on the British Isles Lupus Assessment Group (BILAG) index by at least one severity grade (Severe disease (BILAG A score) must drop to at least moderate (B or better) and B must drop to at least mild (C or not present). Also, there must be no increase in any other BILAG organ scores, no increase in The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and no increase in the physician's global assessment (PGA) by more than 10% of the scale. Furthermore, there may no off protocol medication increases. Note on all scales mentioned a higher score signifies greater disease activity. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Systemic Lupus Erythematosus Responder Index (SRI) 4
Description
This is a landmark analysis of percentage of patients who meet the following response criteria: Compared to baseline there must be a 4 point decrease in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), no increase in The British Isles Lupus Assessment Group (BILAG) Index score and no more of an increase in Physician's Global Assessment (PGA) than 10% of the scale. As assessed here, there must also be no off protocol increase in medications. All scales signify worsening disease when scores increase. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76.
Time Frame
24 weeks
Title
SRI Component Analyses: 4 Point Drop in SLEDAI
Description
This is a landmark analysis of percentage of patients who, compared to baseline, have a 4 point drop in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). A 4 point decrease signifies a clinically significant decrease in disease activity as reported in many studies and as commonly used as a clinical endpoint in trials. SLEDAI could range 0-105 but is rarely greater than 20.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with SLE meeting the 1997 ACR Classification Criteria Evidence of positive ANA or anti-dsDNA within one year of screening SLEDAI ≥4 or ≥1 BILAG A or B at screening, despite standard of care Exclusion Criteria: Leukopenia (WBC <2.000/mm3) or lymphopenia (lymphocytes < 300/mm3) AST or ALT >3 times above normal cut off values Acute lupus nephritis defined as class II, IV or V nephritis diagnosed within 6 months or prot/creat > 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis Active CNS lupus affecting mental status Pregnancy or breast feeding Current requirement for anticoagulation Contraindication to aspirin or dipyridamole, including history of recent or severe GI bleeding, hemoglobin <9 mg/dL, platelet count of <30,000 /mm3 or unstable platelet count Any other medical condition, whether or not related to lupus which, in the opinion of the investigator would render the patient inappropriate or too unstable to complete the study protocol Inability or unwillingness to understand and/or sign informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katherine Thanou, MD
Organizational Affiliation
Oklahoma Medical Research Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oklahoma Medical Research Foundation
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Those who wish access to this data may contact Joan Merrill at joan-merrill@omrf.org for further information
IPD Sharing Time Frame
The data will be available on or before June 1 2021
IPD Sharing Access Criteria
For de-identified data only: Please submit a two page request describing the research you wish to do and the investigators credentials and current employment. This will be reviewed by our cohort advisory board and IRB prior to release.
Citations:
PubMed Identifier
21437870
Citation
Kyttaris VC, Zhang Z, Kampagianni O, Tsokos GC. Calcium signaling in systemic lupus erythematosus T cells: a treatment target. Arthritis Rheum. 2011 Jul;63(7):2058-66. doi: 10.1002/art.30353.
Results Reference
background
PubMed Identifier
33687069
Citation
Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
Results Reference
derived

Learn more about this trial

Dipyridamole Assessment for Flare Reduction in Systemic Lupus Erythematosus (SLE)

We'll reach out to this number within 24 hrs