Maintenance Versus Reduction of Immunosuppression for Renal Transplant Patients Hospitalized With COVID-19 Disease

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Withdrawn
• CT.gov ID: NCT04420364
• Collaborator: (none)
• Enrollment: 0
• Arms: 2
• Actual Duration (Days): 1

Study Details

Study Description

Brief Summary

This will be a randomized trial of maintenance versus reduction in immunosuppression in adult patients (age >18 years old) with functioning renal transplants admitted to hospital with confirmed COVID-19 disease.

Condition or Disease	Intervention/Treatment	Phase
COVID; Kidney Transplant; Complications; Immunosuppression	Other: Maintenance or reduction of immunosuppression	Phase 2/Phase 3

Detailed Description

The optimal management of immunosuppression in renal transplant patients with COVID-19 disease is unclear. On one hand, many centers advocate reduction of immunosuppression in infected patients, with the rationale that such an approach will unleash the anti-viral T-cell response. However, on the other hand, some centers advocate there may be rationale to maintain baseline immunosuppression in order to mitigate against development of an uncontrolled over-activation of the immune response. The investigators propose to address this knowledge gap by performing a randomized clinical trial that will test formal comparisons of maintenance versus reduction in immunosuppression.

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Single-blind, parallel-group, randomized, active-controlled trialSingle-blind, parallel-group, randomized, active-controlled trial
• Masking: Single (Outcomes Assessor)
• Masking Description: This is a single-blind trial, in that only the assessor will be blinded to the treatment assignment.
• Primary Purpose: Treatment
• Official Title: Maintenance Versus Reduction of Immunosuppression for Renal Transplant Patients Hospitalized With COVID-19 Disease
• Actual Study Start Date: May 3, 2021
• Actual Primary Completion Date: May 4, 2021
• Actual Study Completion Date: May 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maintenance of Immunosuppression Maintenance of immunosuppression (defined as no change to pre-admission immunosuppression, or reduction in anti-metabolite by up to 50% (to a minimum of MMF 500 mg per day or azathioprine 50 mg per day)	Other: Maintenance or reduction of immunosuppression; Maintenance versus reduction of immunosuppression
Active Comparator: Reduction of Immunosuppression Reduction of immunosuppression (defined as anti-metabolite withdrawal plus reduction of tacrolimus or cyclosporin, to a minimum target trough concentration of 3 ng/mL for tacrolimus and 50 ng/mL for cyclosporin).	Other: Maintenance or reduction of immunosuppression; Maintenance versus reduction of immunosuppression

Outcome Measures

Primary Outcome Measures

1. Change in IL-6 concentration from baseline to day 7 [baseline to day 7]

Secondary Outcome Measures

1. Change in IL-6 concentration from baseline to day 28 [Baseline to day 28]

2. Change in T cell response to SARS-CoV-2 [Baseline to day 7 and day 28]

3. Change in titer of serum anti-SARS-CoV-2 antibodies [Baseline to day 7 and day 28]

4. Change in COVID-19 disease severity score (range 1 to 8; higher worse) [Through day 28]

5. Proportion of patients needing non-invasive ventilation or intubation [Through day 28]

6. Proportion of patients developing ANC < 500 cells per microliter [Through day 28]

7. Proportion of patients developing lymphopenia < 400 cells per microliter [Through day 28]

8. Length of hospital stay [Through day 28]

9. Proportion of patients developing biopsy-proven acute rejection [Through day 28]

10. In-hospital and 28-day mortality [Through day 28]

11. Adverse and serious adverse events [Through day 28]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults ≥18 years

• COVID positive by RT-PCR or serology

• ≥ 6 months post-transplant

• use of anti-metabolite (mycophenolate or azathioprine) and calcineurin inhibitor (cyclosporin or tacrolimus)

• informed consent; first admission during study period

• participation within 72 hours of hospitalization

Exclusion Criteria:

• ICU care or need for invasive ventilation or use of pressors at screening/randomization

• COVID-19 disease severity score more than 5 at screening/randomization

• Known donor specific antibody

• eGFR <20ml/min/1.73m2

• hematocrit <24%

• biopsy proven and treated rejection within last 3 months

• institutionalized individuals (prisoners)

• pregnancy

• participation in another clinical study with an investigational medicinal product within 30 days or within 5 half-lives of such, whichever is longer, prior to randomization and during the study

• any other conditions, which, in the opinion of the investigator would make the subject unsuitable.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Jamil Azzi, MD, PhD, Birgham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Finnian McCausland, Associate Physician, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT04420364
• Other Study ID Numbers: 2020P001516
• First Posted: Jun 9, 2020
• Last Update Posted: May 4, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Study Results

No Results Posted as of May 4, 2022