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

Phase 2

Withdrawn

• Conditions: Kidney Transplant; Complications; Immunosuppression; COVID

• 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.

Study Timeline

• Study First Submitted: 2020-06-04
• Study First Submitted QC: 2020-06-05
• Study First Posted: 2020-06-09
• Study Start: 2021-05-03
• Primary Completion: 2021-05-04
• Study Completion: 2021-05-04
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-03
• Last Update Posted: 2022-05-04

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• Status: WITHDRAWN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

Primary Outcome Measures

Name	Time	Method
Change in IL-6 concentration from baseline to day 7	baseline to day 7

Secondary Outcome Measures

Name	Time	Method
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
Proportion of patients developing ANC < 500 cells per microliter	Through day 28
Proportion of patients developing biopsy-proven acute rejection	Through day 28
Adverse and serious adverse events	Through day 28
Length of hospital stay	Through day 28
In-hospital and 28-day mortality	Through 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 lymphopenia < 400 cells per microliter	Through day 28
Change in titer of serum anti-SARS-CoV-2 antibodies	Baseline to day 7 and day 28