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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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COVID, Kidney Transplant; Complications, Immunosuppression

Intervention / Treatment
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* Other: Maintenance or reduction of immunosuppression


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-blind, parallel-group, randomized, active-controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maintenance of Immunosuppression<br>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<br>* Maintenance versus reduction of immunosuppression<br>|
| Active Comparator: Reduction of Immunosuppression<br>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<br>* Maintenance versus reduction of immunosuppression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IL-6 concentration from baseline to day 7 |  | baseline to day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IL-6 concentration from baseline to day 28 |  | Baseline to day 28 | 
| Change in T cell response to SARS-CoV-2 |  | Baseline to day 7 and day 28 | 
| Change in titer of serum anti-SARS-CoV-2 antibodies |  | Baseline to day 7 and day 28 | 
| Change in COVID-19 disease severity score (range 1 to 8; higher worse) |  | Through day 28 | 
| Proportion of patients needing non-invasive ventilation or intubation |  | Through day 28 | 
| Proportion of patients developing ANC < 500 cells per microliter |  | Through day 28 | 
| Proportion of patients developing lymphopenia < 400 cells per microliter |  | Through day 28 | 
| Length of hospital stay |  | Through day 28 | 
| Proportion of patients developing biopsy-proven acute rejection |  | Through day 28 | 
| In-hospital and 28-day mortality |  | Through day 28 | 
| Adverse and serious adverse events |  | Through day 28 |