Clinical trial NCT04420364: Maintenance Versus Reduction of Immunosuppression for Renal Transplant Patients Hospitalized With COVID-19 Disease
Official title: Maintenance Versus Reduction of Immunosuppression for Renal Transplant Patients Hospitalized With COVID-19 Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: COVID
Kidney Transplant; Complications
Immunosuppression
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-blind, parallel-group, randomized, active-controlled trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in IL-6 concentration from baseline to day 7
timeFrame: baseline to day 7
Secondary outcomes:
measure: Change in IL-6 concentration from baseline to day 28
timeFrame: Baseline to day 28
measure: Change in T cell response to SARS-CoV-2
timeFrame: Baseline to day 7 and day 28
measure: Change in titer of serum anti-SARS-CoV-2 antibodies
timeFrame: Baseline to day 7 and day 28
measure: Change in COVID-19 disease severity score (range 1 to 8; higher worse)
timeFrame: Through day 28
measure: Proportion of patients needing non-invasive ventilation or intubation
timeFrame: Through day 28
measure: Proportion of patients developing ANC < 500 cells per microliter
timeFrame: Through day 28
measure: Proportion of patients developing lymphopenia < 400 cells per microliter
timeFrame: Through day 28
measure: Length of hospital stay
timeFrame: Through day 28
measure: Proportion of patients developing biopsy-proven acute rejection
timeFrame: Through day 28
measure: In-hospital and 28-day mortality
timeFrame: Through day 28
measure: Adverse and serious adverse events
timeFrame: Through day 28
Other outcomes:
Locations:
Study officials:
affiliation: Birgham and Women's Hospital
name: Jamil Azzi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: