COVID, Immunosuppression, Kidney Transplant; Complications
Conditions
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.
Interventions
OTHERMaintenance or reduction of immunosuppression
Maintenance versus reduction of immunosuppression
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
This is a single-blind trial, in that only the assessor will be blinded to the treatment assignment.
Intervention model description
Single-blind, parallel-group, randomized, active-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in IL-6 concentration from baseline to day 7 | baseline to day 7 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Change in IL-6 concentration from baseline to day 28 | Baseline to 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 |
| Proportion of patients developing lymphopenia < 400 cells per microliter | Through day 28 |
Outcome results
None listed