Clinical trial NCT04123275: Prediction on Time to Death in Potential Controlled Donation After Circulatory Death (cDCD) Donors (DCD III Study)
Official title: 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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tissue and Organ Procurement
Keywords: Validation studies
Withholding treatment
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2019-10-10
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration (in minutes) on time to circulatory death after withdrawal of life-sustaining treatment, in cDCD patients
timeFrame: 36 months
Secondary outcomes:
measure: Incidence of circulatory death in 60 minutes
timeFrame: 36 months
measure: Incidence of circulatory death in 120 and 180 minutes
timeFrame: 36 months
measure: Doses analgesia
timeFrame: 36 months
measure: Doses sedation
timeFrame: 36 months
measure: Incidence of withdrawal of endotracheal tube
timeFrame: 36 months
Other outcomes:
Locations:
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Tilburg
country: Netherlands
facility: ETZ
city: Zwolle
country: Netherlands
facility: Isala clinics
Study officials:
References:
citation: 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.
citation: 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.