PGDT in Patients Undergoing Kidney Transplant

Kidney Transplant Clinical Trial

— PGDT  

Official title:

Hemodynamic Optimization With Perioperative Gold Directed Therapy (PGDT) in Kidney Transplant

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05035537
• Other study ID #: PGDT2017
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2018
• Est. completion date: June 30, 2023

Study information

• Verified date: January 2023
• Source: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Contact: Cristiana Laici, MD
• Phone: 0039 051 2143101
• Email: cristiana.laici[@]aosp.bo.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a multicentric randomized controlled trial comparing two groups of patients undergoing single or dual kidney transplantation from deceased donors. To reduce perioperative complications optimal fluid management is essential in patients undergoing kidney transplantation. Heart rate, Medium Arterial Pressure (MAP), Central Venous Pressure (CVP), and urine output have been proposed in the literature to guide perioperative fluid therapy. These criteria are routinely applied in clinical practice; however these criteria have shown low sensitivity and poor predictive of postoperative complication, especially if used alone. The traditional approach in renal transplantation is the volume infusion guided whit CVP to the point of no further fluid responsiveness, but this can lead to excess fluid which can damage the endothelial glycocalyx and lead to organ failure for a fluid shift into the interstitial space.

As a way to reduce postoperative complications in surgical patients, in recent years, several studies have examined Perioperative Goal Directed Therapy (PGDT) as fluid administration guided by optimization of preload with the use of algorithms based on fluids, inotropes and/or vasopressors to achieve a certain goal in stroke volume (SV), cardiac index (CI), or oxygen delivery (DO2). However results regarding the potential role of PGDT cannot be considered definitive, because the various studies on the subject have not all conformed to the same methods and have not uniformly applied the same measurements, so their results regarding the potential role of PGDT cannot be considered definitive.

The aim of this work is to compare the effects of PGDT with conventional fluid therapy in patients undergoing kidney transplantation achievable through implementation of the non invasive monitoring.

Description:

To reduce perioperative complications optimal fluid management is essential in patients undergoing kidney transplantation. Heart rate, Medium Arterial Pressure (MAP), Central Venous Pressure (CVP), and urine output have been proposed in the literature to guide perioperative fluid therapy. These criteria are routinely applied in clinical practice; however these criteria have shown low sensitivity and poor predictive of postoperative complication, especially if used alone. The traditional approach in renal transplantation is the volume infusion guided whit CVP to the point of no further fluid responsiveness, but this can lead to excess fluid which can damage the endothelial glycocalyx and lead to organ failure for a fluid shift into the interstitial space.

As a way to reduce postoperative complications in surgical patients, in recent years, several studies have examined Perioperative Goal Directed Therapy (PGDT) as fluid administration guided by optimization of preload with the use of algorithms based on fluids, inotropes and/or vasopressors to achieve a certain goal in stroke volume (SV), cardiac index (CI), or oxygen delivery (DO2). However results regarding the potential role of PGDT cannot be considered definitive, because the various studies on the subject have not all conformed to the same methods and have not uniformly applied the same measurements, so their results regarding the potential role of PGDT cannot be considered definitive.

The aim of this work is to compare the effects of PGDT with conventional fluid therapy in patients undergoing kidney transplantation achievable through implementation of the non invasive monitoring.

MATERIAL AND METHODS. This study is a multicentric randomized controlled trial comparing two groups of patients undergoing single or dual kidney transplantation from deceased donors. All patients who will meet eligibility criteria will be randomised, using a computer generated randomization list, to either Group 1 (PGDT, intervention group) where minimally invasive continuous CI monitor (Edwards ClearSight) will be used to guide a goal directed fluid administration protocol, and Group 2 (control) managed according to local and international best practice guidelines using standard hemodynamic monitoring.

STUDY DESIGN. The study protocol will be developed across the intraoperative and postoperative periods. In the intraoperative phase all standard monitored parameters such as EKG, SpO2 (oxygen saturation by pulse oximetry), airway pressure etc. will be the same for both groups. Where ClearSight minimally invasive monitoring will be used (Group 1), hemodynamic optimization goals will be as follows: CI ≥ 2.5 L/min/m2 and the SVV <10%. Sequential interventions used to reach the hemodynamic goals are regulated by a flow-chart provided in the study protocol. In Group 2 conventional static hemodynamic parameters (CVP, IBP) are evaluated to achieve an intraoperative MAP ≥ 70 mmHg with corrective actions (fluids, vasoactive agents) implemented according to the recommendations of good clinical practice and international guidelines. Both groups will receive standard induction immunosuppression according to our centre's practice as well as corticosteroid bolus (or two boluses if a dual kidney transplant was performed) before graft reperfusion. In the postoperative period all patients will be transferred to a dedicated post-surgical intensive care unit. The same standardized fluid therapy regimen will be adopted across both groups. Patient data will be prospectively collected, according to the study protocol, by designated personnel using a digital case report form.

SAMPLE SIZE CALCULATION AND STATISTICAL ANALYSIS. The investigators speculate that in order to detect a minimum reduction in the primary outcome of at least 18%, considering a power of 80% and a type I error of 5%, a total of 200 patients would be needed (100 per group). All results will be summarized in the text as means, unless differently stated each time with measures of variability expressed using mean and standard deviation. When reporting medians, measures of variability will be indicated as interquartile range, minimum value, and maximum value. Difference between population means will be obtained using the 2-sample t test; difference between population proportions will be obtained with the chi-square test and Fisher's exact test. Graft survival will be calculated from the date of kidney transplant to the date of last follow-up evaluation, graft loss, or patient death. P-values below or equal to 0.05 are considered as statistically significant.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 30, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• age > 18 years,

• first single- or dual-kidney transplant from a deceased donor,

• absence of atrial fibrillation or other severe arrythmia,

• ASA (American Society of Anesthesiologists) class III-IV,

• presence of written expression of consent.

Exclusion Criteria:

• patients receiving a retransplant,

• patients receiving a combined liver-kidney transplant,

• patients receiving a transplant from a living donor .

Related Conditions & MeSH terms

• Complications
• Kidney Transplant

Intervention

Procedure:
• PGDT
The minimally invasive continuous CI monitor (Edwards ClearSight) was used to guide an optimization of preload with the use of algorithms based on fluids, inotropes and/or vasopressors to achieve a certain goal in medium arterial pressure (MAP), cardiac index (CI) and stroke volume variation (SVV)

Locations

Country	Name	City	State
Italy	SOD Anestesia e Rianimazione dei Trapianti e Chirurgia Maggiore, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi	Ancona
Italy	Dipartimento di Anestesia e Rianimazione - Città della salute e della scienza, Torino	Torino

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Azienda Ospedaliero-Universitaria di Bologna

Country where clinical trial is conducted

Italy, 

References & Publications (15)

Ameloot K, Palmers PJ, Malbrain ML. The accuracy of noninvasive cardiac output and pressure measurements with finger cuff: a concise review. Curr Opin Crit Care. 2015 Jun;21(3):232-9. doi: 10.1097/MCC.0000000000000198. — View Citation

Biancofiore G, Cecconi M, Rocca GD. A web-based Italian survey of current trends, habits and beliefs in hemodynamic monitoring and management. J Clin Monit Comput. 2015 Oct;29(5):635-42. doi: 10.1007/s10877-014-9646-7. Epub 2014 Dec 12. — View Citation

Fischer MO, Fiant AL, Boutros M, Flais F, Filipov T, Debroczi S, Pasqualini L, Rhanem T, Gerard JL, Guittet L, Hanouz JL, Alves A, Parienti JJ; PANEX3 study group. Perioperative hemodynamic optimization using the photoplethysmography in colorectal surgery (the PANEX3 trial): study protocol for a randomized controlled trial. Trials. 2016 Mar 22;17:159. doi: 10.1186/s13063-016-1278-4. — View Citation

Gomez-Izquierdo JC, Feldman LS, Carli F, Baldini G. Meta-analysis of the effect of goal-directed therapy on bowel function after abdominal surgery. Br J Surg. 2015 May;102(6):577-89. doi: 10.1002/bjs.9747. Epub 2015 Mar 11. — View Citation

Hamilton MA, Cecconi M, Rhodes A. A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients. Anesth Analg. 2011 Jun;112(6):1392-402. doi: 10.1213/ANE.0b013e3181eeaae5. Epub 2010 Oct 21. — View Citation

Jhanji S, Thomas B, Ely A, Watson D, Hinds CJ, Pearse RM. Mortality and utilisation of critical care resources amongst high-risk surgical patients in a large NHS trust. Anaesthesia. 2008 Jul;63(7):695-700. doi: 10.1111/j.1365-2044.2008.05560.x. Epub 2008 May 16. — View Citation

Lobo SM, Rezende E, Knibel MF, Silva NB, Paramo JA, Nacul FE, Mendes CL, Assuncao M, Costa RC, Grion CC, Pinto SF, Mello PM, Maia MO, Duarte PA, Gutierrez F, Silva JM Jr, Lopes MR, Cordeiro JA, Mellot C. Early determinants of death due to multiple organ failure after noncardiac surgery in high-risk patients. Anesth Analg. 2011 Apr;112(4):877-83. doi: 10.1213/ANE.0b013e3181e2bf8e. Epub 2010 Jun 8. — View Citation

Pearse RM, Harrison DA, James P, Watson D, Hinds C, Rhodes A, Grounds RM, Bennett ED. Identification and characterisation of the high-risk surgical population in the United Kingdom. Crit Care. 2006;10(3):R81. doi: 10.1186/cc4928. Epub 2006 Jun 2. — View Citation

Perilli V, Aceto P, Sacco T, Modesti C, Ciocchetti P, Vitale F, Russo A, Fasano G, Dottorelli A, Sollazzi L. Anaesthesiological strategies to improve outcome in liver transplantation recipients. Eur Rev Med Pharmacol Sci. 2016 Jul;20(15):3172-7. — View Citation

Sangkum L, Liu GL, Yu L, Yan H, Kaye AD, Liu H. Minimally invasive or noninvasive cardiac output measurement: an update. J Anesth. 2016 Jun;30(3):461-80. doi: 10.1007/s00540-016-2154-9. Epub 2016 Mar 9. — View Citation

Scolletta S, Franchi F, Romagnoli S, Carla R, Donati A, Fabbri LP, Forfori F, Alonso-Inigo JM, Laviola S, Mangani V, Maj G, Martinelli G, Mirabella L, Morelli A, Persona P, Payen D; Pulse wave analysis Cardiac Output validation (PulseCOval) Group. Comparison Between Doppler-Echocardiography and Uncalibrated Pulse Contour Method for Cardiac Output Measurement: A Multicenter Observational Study. Crit Care Med. 2016 Jul;44(7):1370-9. doi: 10.1097/CCM.0000000000001663. — View Citation

Stover JF, Stocker R, Lenherr R, Neff TA, Cottini SR, Zoller B, Bechir M. Noninvasive cardiac output and blood pressure monitoring cannot replace an invasive monitoring system in critically ill patients. BMC Anesthesiol. 2009 Oct 12;9:6. doi: 10.1186/1471-2253-9-6. — View Citation

van der Spoel AG, Voogel AJ, Folkers A, Boer C, Bouwman RA. Comparison of noninvasive continuous arterial waveform analysis (Nexfin) with transthoracic Doppler echocardiography for monitoring of cardiac output. J Clin Anesth. 2012 Jun;24(4):304-9. doi: 10.1016/j.jclinane.2011.09.008. — View Citation

Vincent JL, Rhodes A, Perel A, Martin GS, Della Rocca G, Vallet B, Pinsky MR, Hofer CK, Teboul JL, de Boode WP, Scolletta S, Vieillard-Baron A, De Backer D, Walley KR, Maggiorini M, Singer M. Clinical review: Update on hemodynamic monitoring--a consensus of 16. Crit Care. 2011 Aug 18;15(4):229. doi: 10.1186/cc10291. — View Citation

Walsh SR, Tang T, Bass S, Gaunt ME. Doppler-guided intra-operative fluid management during major abdominal surgery: systematic review and meta-analysis. Int J Clin Pract. 2008 Mar;62(3):466-70. doi: 10.1111/j.1742-1241.2007.01516.x. Epub 2007 Nov 21. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hospital stay	The primary study outcome was to investigate whether the adoption of a PGDT protocol would reduce overall hospital stay.	Through study completion, an average of 6 months
Secondary	Incidence of postoperative surgical and medical complications	Secondary endpoint was the detection of any significant change in the incidence of postoperative surgical (Clavien-Dindo Classification= 3) and medical (pulmonary or cardiovascular) complications	Through study completion, an average of 6 months
Secondary	Incidence of delayed graft function and graft loss	Secondary endpoint was the detection of any significant change in the incidence of delayed graft function and graft loss	Through study completion, an average of 6 months
Secondary	ICU stay	Secondary endpoint was the detection of any significant change in the ICU length of stay	Through study completion, an average of 6 months