Cyclosporine vs Steroids in DRESS

DRESS Syndrome Clinical Trial

Official title:

A Randomized Controlled Pilot Trial of Cyclosporine vs Steroids in DRESS

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04988256
• Other study ID #: HS-20-00118
• Status: Enrolling by invitation
• Phase: Early Phase 1
• Start date: September 27, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: November 2023
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Current treatments for patients with drug reaction with eosinophilia and systemic symptoms (DRESS) include supportive care, steroids and cyclosporine. No randomized controlled trial (RCT) exists in comparing these treatments and all available literature comes in the form of case reports and case series. These two treatments are considered standard of care and this trial seeks only to compare outcomes of DRESS between these two therapies. No additional labs, therapies or procedures will be used apart from those that are routinely done for patients with this diagnosis.

This will be a pilot study to determine efficacy of the two therapies with particular endpoints in mind so that the investigators can study the safety of these two therapies in patients with DRESS.

Data suggests a potential benefit for adults with DRESS using either steroids or cyclosporine but the investigators are seeking a comparison of efficacy of these two therapies. The study population will include adults with a Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) score of greater than 4 (i.e. a likely diagnosis of DRESS). The investigators will exclude patients with sepsis, active Hepatitis B or C, active tuberculosis, a documented allergy to steroids or cyclosporine, and patients with an estimated glomerular filtration rate (eGFR) < 30 (unless on dialysis in which case the participants will be included).

Description:

Current treatments for patients with drug reaction with eosinophilia and systemic symptoms (DRESS) include supportive care, steroids, cyclosporine and to a lesser extent, intravenous immunoglobulin (IVIG). Regarding IVIG, a recent case series suggests no improved benefit in adults. No randomized controlled trial (RCT) exists in comparing these treatments and all available literature comes in the form of case reports and case series. These two treatments are considered standard of care and this trial seeks only to compare outcomes of DRESS between these two therapies. No additional labs, therapies or procedures will be used apart from those that are routinely done for patients with this diagnosis.

This will be a pilot study to determine efficacy of the two therapies with particular endpoints in mind so that the investigators can study the safety of these two therapies in patients with DRESS. Hopefully, this study will allow the investigators to better power a full prospective trial in the future.

This is a potentially life-threatening severe cutaneous adverse reaction (SCAR) with significant potential morbidity. Data suggests a potential benefit for adults with DRESS using either steroids or cyclosporine but the investigators are seeking a comparison of efficacy of these two therapies. The study population will include adults with a Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) score of greater than 4 (i.e. a likely diagnosis of DRESS). The investigators will exclude patients with sepsis, active Hepatitis B or C, active tuberculosis, a documented allergy to steroids or cyclosporine, and patients with an estimated glomerular filtration rate (eGFR) < 30 (unless on dialysis in which case the participants will be included).

Participants will be randomized using a randomization protocol at all sites. Primary endpoints will include percentage of participants with complete or near complete resolution of organ involvement as well as erythema resolution at day 7 and day 30.

Secondary endpoints will be:

1. fever presence, resolution of facial edema, resolution of pruritus, lymphadenopathy, eosinophil count at days 7 and 30

2. days of hospitalization

3. mortality at days 7, 30 and 90

4. viral reactivation at days 30, 60 and 90

5. those with autoimmune development by day 30 and day 90

6. 30 day re-admission rate.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 50
• Est. completion date: June 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults with a RegiSCAR score of greater than 4 (i.e a likely diagnosis of DRESS)

Exclusion Criteria:

• Active sepsis

• Active hepatitis B or C

• Active tuberculosis

• Documented allergy to steroids or cyclosporine

• Estimated glomerular filtration rate (eGFR) < 30 (unless on dialysis, in which case they will be included)

Related Conditions & MeSH terms

• DRESS Syndrome
• Drug Hypersensitivity Syndrome
• Hypersensitivity
• Syndrome

Intervention

Drug:
• Cyclosporine
Patients randomized to cyclosporine will be treated as mentioned under "Arm/Group Description"
• Methylprednisolone and Prednisone
All patients randomized to steroids will initially be treated with IV methylprednisolone and eventually started on an oral prednisone taper.

Locations

Country	Name	City	State
United States	USC	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with complete or near complete resolution of organ involvement at day 30, on steroid therapy and cyclosporine therapy	Measured by the following quantitative metrics: Creatinine within 1.25x of baseline or upper limit of normal, whichever is higher; Aspartate Aminotransferase (AST) within 1.5x of baseline or upper limit of normal, whichever is higher; Troponin-T, Creatine Kinase Myocardial Band (CK-MB), Pro B-type Natriuretic Peptide (Pro-BNP), and lipase within 1.25x of baseline or upper limit of normal, whichever is higher; Resolution of interstitial pneumonitis on chest x-ray	Day 7
Primary	Percentage of patients with complete or near complete resolution of organ involvement at day 30, on steroid therapy and cyclosporine therapy	Measured by the following quantitative metrics: Creatinine within 1.25x of baseline or upper limit of normal, whichever is higher; Aspartate Aminotransferase (AST) within 1.5x of baseline or upper limit of normal, whichever is higher; Troponin-T, Creatine Kinase Myocardial Band (CK-MB), Pro B-type Natriuretic Peptide (Pro-BNP), and lipase within 1.25x of baseline or upper limit of normal, whichever is higher; Resolution of interstitial pneumonitis on chest x-ray	Day 30
Primary	Percentage of patients with complete or near complete resolution of erythema at day 7, on steroid therapy and cyclosporine therapy	Clinical measurement of erythema	Day 7
Primary	Percentage of patients with complete or near complete resolution of erythema at day 30, on steroid therapy and cyclosporine therapy	Clinical measurement of erythema	Day 30
Secondary	Percentage of patients with resolution of fever	Less than 38 degrees Celsius for at least 24 hours	Day 7
Secondary	Percentage of patients with resolution of fever	Less than 38 degrees Celsius for at least 24 hours	Day 30
Secondary	Percentage of patients with resolution of facial edema	Clinical resolution of edema for at least 24 hours	Day 7
Secondary	Percentage of patients with resolution of facial edema	Clinical resolution of edema for at least 24 hours	Day 30
Secondary	Percentage of patients with resolution of pruritus	Resolution for at least 24 hours	Day 7
Secondary	Percentage of patients with resolution of pruritus	Resolution for at least 24 hours	Day 30
Secondary	Percentage of patients with resolution of lymphadenopathy	Clinical resolution of lymphadenopathy for at least 24 hours	Day 7
Secondary	Percentage of patients with resolution of lymphadenopathy	Clinical resolution of lymphadenopathy for at least 24 hours	Day 30
Secondary	Absolute eosinophil proportion compared to peak value	Proportion of absolute eosinophils	Day 7
Secondary	Absolute eosinophil proportion compared to peak value	Proportion of absolute eosinophils	Day 30
Secondary	Patients with autoimmune disease development	Measured by titers of autoimmune markers (Antinuclear Antibody (ANA), Thyroid Stimulating Hormone (TSH)) compared to baseline	Day 30
Secondary	Patients with autoimmune disease development	Measured by titers of autoimmune markers (Antinuclear Antibody (ANA), Thyroid Stimulating Hormone (TSH)) compared to baseline	Day 90
Secondary	Total days of hospitalization after initial dermatology consult	Number of days	0-120 days
Secondary	Viral reactivation	Measured by titers of Human Herpesvirus 6 (HHV6), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV)	Day 30
Secondary	Viral reactivation	Measured by titers of Human Herpesvirus 6 (HHV6), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV)	Day 60
Secondary	Viral reactivation	Measured by titers of Human Herpesvirus 6 (HHV6), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV)	Day 90
Secondary	Mortality	Proportion of patient mortality	Day 7
Secondary	Mortality	Proportion of patient mortality	Day 30
Secondary	Mortality	Proportion of patient mortality	Day 90
Secondary	30-day readmission rate	Proportion of patients re-admitted to the hospital within 30 days of discharge	Day 30