MedPath

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

Phase 2
Withdrawn
Conditions
Kidney Transplant; Complications
Immunosuppression
COVID
Interventions
Other: Maintenance or reduction of immunosuppression
Registration Number
NCT04420364
Lead Sponsor
Brigham and Women's Hospital
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.

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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Reduction of ImmunosuppressionMaintenance or reduction of immunosuppressionReduction 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).
Maintenance of ImmunosuppressionMaintenance or reduction of immunosuppressionMaintenance 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)
Primary Outcome Measures
NameTimeMethod
Change in IL-6 concentration from baseline to day 7baseline to day 7
Secondary Outcome Measures
NameTimeMethod
Length of hospital stayThrough day 28
Change in IL-6 concentration from baseline to day 28Baseline to day 28
Change in T cell response to SARS-CoV-2Baseline to day 7 and day 28
Proportion of patients developing ANC < 500 cells per microliterThrough day 28
Proportion of patients developing biopsy-proven acute rejectionThrough day 28
Adverse and serious adverse eventsThrough day 28
In-hospital and 28-day mortalityThrough 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 intubationThrough day 28
Proportion of patients developing lymphopenia < 400 cells per microliterThrough day 28
Change in titer of serum anti-SARS-CoV-2 antibodiesBaseline to day 7 and day 28
© Copyright 2025. All Rights Reserved by MedPath