Prediction on Time to Death in Potential Controlled Donation After Circulatory Death (cDCD) Donors (DCD III Study) (DCDIII)

DCD III Study: a Multicentre Prospective Study to Identify Parameters Predicting Time to Death in Controlled Circulatory Death (cDCD) Donors and Prospective Validation of Previous Derived Prediction Models on Time to Death.

A considerable number of potential cDCD donors do not convert into actual organ donors because circulatory arrest does not occur within the predefined timeframe of warm ischemia after withdrawal of life-sustaining treatment. The main objective of this study is to determine parameters predicting time to death in potential cDCD patients.

Study Overview

• Status: Completed
• Conditions: Tissue and Organ Procurement
• Intervention / Treatment: Other: No intervention wil be done. Patient characteristics and the standard care before and after withdrawal of life-sustaining treatment in all potential cDCD donors, will be studied. .

Detailed Description

Controlled donation after circulatory death (cDCD) is a major source of organs for transplantation. Even though there is a well-established cDCD program in the Netherlands, there is still a considerable number of potential donors not being converted into actual organ donors. A potential cDCD donor poses considerable challenges in terms of a) identification of those dying within the predefined timeframe of warm ischemia, after withdrawal of life-sustaining treatment to circulatory arrest, b) managing them appropriately within the framework and resources of the intensive care unit, c) dealing with family expectations especially when failure to donation occurs, and d) efficient utilization of the organ procurement teams.

Factors associated with early circulatory collapse after treatment withdrawal include a younger age, non-triggered modes of artificial ventilation, high FiO2, the use of inotropes, and a low arterial pH. Another important factor which could influence the donor potential is end-of-life treatment. The practice of withdrawal of life support treatment (WLST) is highly variable between ICU's and countries. This influences the dying process and can thus have a large influence on the onset of cardio respiratory arrest. There is also wide variation in the use and dosage of additional sedation and analgesia during WLST and controversy exists regarding hastening or slowing down death.

Several attempts have been made to develop models to predict the time between treatment withdrawal and circulatory arrest, as this is crucial to a) proceed with organ donation, and b) the quality of the harvested organs. The selected patients however, where not always restricted to potential candidates for cDCD organ donation as patients with cancer and severe infection were also included.

Objective: Objectives of this study are: a) To determine parameters predicting time to death in potential cDCD patients b) To validate and update previous predicting models on time to death after withdrawal of life-sustaining treatment. c) To assess variation in withdrawal of life-sustaining treatment in the Netherlands and its influence on post mortal organ donor potential and actual post mortal organ donors.

Design and setting: Multicenter, observational, prospective cohort study of all potential cDCD patients of 3 university and 3 teaching hospitals in the Netherlands with diverse focus of attention

Methods: All potential cDCD patients participating in the cDCD protocol as defined by the Dutch Transplant Foundation admitted at the Intensive Care unit, will be included.

Participants: Mechanically ventilated ICU patients aged between 18 to 75 years. Brain dead patients will be excluded.

• Study Type: Observational
• Enrollment (Actual): 400

Contacts and Locations

Study Locations

• Netherlands
  • Den Bosch, Netherlands, 5223GZ
    • Jeroen Bosch Hospital
  • Groningen, Netherlands, 9713
    • University Medical Center Groningen
  • Nijmegen, Netherlands, 5600HB
    • Radboud University Medical Center
  • Rotterdam, Netherlands, 3015GD
    • Erasmus Medical Center
  • Tilburg, Netherlands, 5022GC
    • ETZ
  • Zwolle, Netherlands, 8025AB
    • Isala Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All mechanically ventilated patients admitted at the Intensive Care Unit, aged between 18 and 75 years old who are eligible to enter the organ procurement protocol of the Dutch Transplant Foundation.

Description

Inclusion Criteria:

• mechanically ventilated patients
• aged between 18 and 75 years old, where further treatment is futile.
• patients should meet the criteria of potential cDCD donors as defined by the Dutch Transplant Foundation

Exclusion Criteria:

• non-intubated patients
• younger than 18 years old
• brain dead patients

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration (in minutes) on time to circulatory death after withdrawal of life-sustaining treatment, in cDCD patients	Development of a prediction tool to detect time to circulatory death (in minutes) in controlled donation after circulatory death patients (cDCD)	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of circulatory death in 60 minutes	Number of patients with circulatory death within 60 minutes	36 months
Incidence of circulatory death in 120 and 180 minutes	Number of patients when circulatory death occurs within the timeframe of 120 and 180 minutes	36 months
Doses analgesia	Doses analgesia provided before and during withdrawal of life support in milligrams per hour	36 months
Doses sedation	Doses sedation provided before and during withdrawal of life support in milligrams per hour	36 months
Incidence of withdrawal of endotracheal tube	Number of endotracheal tubes removed	36 months

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Publications and helpful links

General Publications

• Kotsopoulos A, Vos P, Witjes M, Volbeda M, Franke H, Epker J, Sonneveld H, Simons K, Bronkhorst E, Mullers R, Jansen N, van der Hoeven H, Abdo WF. Prospective Multicenter Observational Cohort Study on Time to Death in Potential Controlled Donation After Circulatory Death Donors-Development and External Validation of Prediction Models: The DCD III Study. Transplantation. 2022 Sep 1;106(9):1844-1851. doi: 10.1097/TP.0000000000004106. Epub 2022 Mar 8.
• Kotsopoulos AMM, Vos P, Jansen NE, Bronkhorst EM, van der Hoeven JG, Abdo WF. Prediction Model for Timing of Death in Potential Donors After Circulatory Death (DCD III): Protocol for a Multicenter Prospective Observational Cohort Study. JMIR Res Protoc. 2020 Jun 23;9(6):e16733. doi: 10.2196/16733.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2015
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 10, 2019

Study Record Updates

• Last Update Posted (Actual): October 10, 2019
• Last Update Submitted That Met QC Criteria: October 9, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Validation studies; Withholding treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Death
• Other Study ID Numbers: nw 2014-36

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