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

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID; Immunosuppression; Kidney Transplant; Complications
• Intervention / Treatment: Other: Maintenance or reduction of immunosuppression

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 Type: Interventional
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Actual): May 4, 2021
• Study Completion (Actual): May 4, 2021

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 2020P001516

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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