Monitoring Organ Donors to Improve Transplantation Results (MOnIToR) trial methodology

Abstract

Background: Despite efforts to increase organ donation, there remain critical shortages in organ donors and organs procured per donor. Our trial is a large-scale, multicentre, randomised controlled trial in brain-dead donors, to compare protocolised care (using minimally invasive haemodynamic monitoring) with usual care. We describe the study design and discuss unique aspects of doing research in this population.

Methods: Our study will randomise brain-dead patients to protocolised or usual care. The primary end point is the number of organs transplanted per donor. Secondary end points include number of transplantable organs per donor, recipient 6-month hospital-free survival time, and the relationship between the level of interleukin-6 and the number and usability of organs transplanted. The primary analysis will be an intention-to-treat analysis; secondary analyses include modified intention-to-treat and as-treated analyses. The study will also compare the ratio of observed to expected number of organs transplanted per donor, by treatment arm, as a secondary end point. Preplanned subgroup analyses include restriction to extended criteria donors, and donors older or younger than 65 years.

Results and conclusions: Several unique challenges for study design and execution can be seen in our trial, and it should generate results that will inform and influence the fields of organ donation and transplantation.

Trial registration: ClinicalTrials.gov NCT00987714.

Figure 1. Monitoring Organ Donors to Improve Transplantation Results intervention algorithm

A 1-day workshop was held in Pittsburgh in the summer of 2007, followed by web conferences in the summer and autumn of 2007. The planning committee consisted of transplantation experts (see Appendix), who developed a consensus-based algorithm for donor resuscitation based on blood pressure (mean arterial pressure [MAP], in mmHg), cardiac index (CI) and pulse pressure variation (PPV).

Figure 2. Modified intention-to-treat (mITT) trial population

All MOnIToR subjects randomly allocated to protocolised care or usual care were considered for mITT. In the protocolised care arm, all subjects who had haemodynamic monitoring and no protocol violation were included in the mITT population. In the usual care arm, subjects without protocol violation were included in the mITT population. MOnIToR = Monitoring Organ Donors to Improve Transplantation Results. * Protocol violation was defined as: subjects not meeting inclusion criteria but enrolled in the study and randomly allocated; subjects in the intervention arm who did not receive haemodynamic monitoring; subjects in the usual care arm who received any form of functional haemodynamic monitoring; or haemodynamic algorithm not followed by the organ procurement coordinators in the intervention arm.

Figure 3. MOnIToR trial per-protocol population

All subjects randomly allocated to either protocolised care or usual care were considered for the per-protocol population. In the protocolised care arm, all subjects for whom adherence criteria were met and the monitor was calibrated prior to use were included in the per-protocol population. All subjects in the usual care arm without protocol deviations were included in the per-protocol population. Monitoring Organ Donors to Improve Transplantation Results *Adherence criteria were defined a priori and will be adjudicated by three study investigators. † Protocol violation was defined as subjects in the usual care arm who received functional haemodynamic monitoring. *‡ Monitor calibration was performed before initiation of the study protocol in the intervention arm.