Ignite Creation Date:
2024-05-06 @ 3:05 PM
Last Modification Date:
2024-10-26 @ 1:42 PM
Study NCT ID:
NCT04514575
Status:
COMPLETED
Last Update Posted:
2021-01-28
First Post:
2020-06-30
Brief Title:
Plasma Transfusion in Major Vascular Surgery
Sponsor:
Naestved Hospital
Organization:
Naestved Hospital
Study Overview
Official Title:
Plasma Transfusion in Major Vascular Surgery a Danish Nationwide Registry Study
Status:
COMPLETED
Status Verified Date:
2021-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
BACKGROUND
Major blood loss is frequent in open repair of ruptured and intact abdominal aortic aneurysm AAA as well as in aorto-bifurcated prosthesis insertion due to aortoiliac occlusive disease
Major blood loss is associated with death post-operative complications and coagulopathy
Data from randomized trials in trauma patients indicate that a high plasma to red blood cell RBC transfusion ratio reduces 30-day mortality
No randomized trial data are available for the AAA population
Observational data demonstrate that a high plasmaRBC transfusion ratio associates to a lower 30 day mortality However the reports are based on small cohorts of 78-165 patients short term outcomes and lack information on major adverse events such as cardiac and respiratory
The Danish Vascular Registry DVR covering 1996-2018 contains data on approx 4400 ruptured and 8200 intact electivesymptomatic AAA repairs and 5400 open aortoiliac repairs due to occlusive disease Expected total count 1997-2018 17000
The Danish Transfusion Database DTDB covering approx 1997-2018 contains information on units of RBCs plasma and platelets transfused A unique patient identification number CPR allows merging of all data set
OBJECTIVE
To identify whether resuscitation with a high plasma to RBC ratio associates to improves survival in open abdominal aortic surgery as compared to a low plasma to RBC-ratio
PICO
Population Open abdominal aortic surgery
Intervention High FFP FFP to RBC unit ratio of 23 to 33 07 - 10
Comparison Low FFP FFP to RBC unit ratio of 03 to 13 00 - 03
Outcome All-cause mortality 90 days following surgery
DATA SOURCES
CPR Danish Civil Registration System DNPR Danish National Patient registry DVR Danish Vascular registry DPDB The Danish national Prescription DataBase
Major blood loss is frequent in open repair of ruptured and intact abdominal aortic aneurysm AAA as well as in aorto-bifurcated prosthesis insertion due to aortoiliac occlusive disease
Major blood loss is associated with death post-operative complications and coagulopathy
Data from randomized trials in trauma patients indicate that a high plasma to red blood cell RBC transfusion ratio reduces 30-day mortality
No randomized trial data are available for the AAA population
Observational data demonstrate that a high plasmaRBC transfusion ratio associates to a lower 30 day mortality However the reports are based on small cohorts of 78-165 patients short term outcomes and lack information on major adverse events such as cardiac and respiratory
The Danish Vascular Registry DVR covering 1996-2018 contains data on approx 4400 ruptured and 8200 intact electivesymptomatic AAA repairs and 5400 open aortoiliac repairs due to occlusive disease Expected total count 1997-2018 17000
The Danish Transfusion Database DTDB covering approx 1997-2018 contains information on units of RBCs plasma and platelets transfused A unique patient identification number CPR allows merging of all data set
OBJECTIVE
To identify whether resuscitation with a high plasma to RBC ratio associates to improves survival in open abdominal aortic surgery as compared to a low plasma to RBC-ratio
PICO
Population Open abdominal aortic surgery
Intervention High FFP FFP to RBC unit ratio of 23 to 33 07 - 10
Comparison Low FFP FFP to RBC unit ratio of 03 to 13 00 - 03
Outcome All-cause mortality 90 days following surgery
DATA SOURCES
CPR Danish Civil Registration System DNPR Danish National Patient registry DVR Danish Vascular registry DPDB The Danish national Prescription DataBase
Detailed Description:
STATISTICAL ANALYSIS PLAN
The primary analysis will be a stratified cox regression model
STRATIFICATION
type of surgerycondition ruptured AAA vs intact AAA vs aorto-iliac occlusive disease source DVR
sex CPR
Center Rigshospitalet vs Gentofte vs Slagelse vs Odense vs Kolding vs Aarhus vs Viborg vs Aalborg source DVR
COVARIATE ADJUSTMENT
calendar time DVR
age CPR
Carlsons comorbidity index score DNPR
Priority Acute vs Sub-acute vs Elective source DVR
Use of anti-thrombotic drugs DPDB A covariate of 4 levels ATC code is noted in parenthesis
1 None vs
2 Anti-platelet therapy
acetylsalicylic acid B01AC06 or
dipyridamole B01AC07 eg persantin or asasantin
3 Anti-platelet therapy thienopyridines-like drugs
clopidogrel B01AC04 or
ticagrelor B01AC24 eg Brilique or
prasugrel B01AC22 eg Efient Comment patients prescribed thienopyridines in combination with aspirin will be included in this thienopyridine anti-platelet group 3
4 Anti-coagulant therapy
Vitamin K antagonists B01AA eg warfarin or phenprocoumon
Low-molecular weight heparine B01AB01-10
Direct thrombin inhibitors B01AE eg PradaxaDabigatran
Direct factor Xa inhibitors B01AF eg RivaroxabanXarelto Comment patients prescribed both anticoagulant- and antiplatelet therapy and will be included in this Anti-coagulant group 4
ADDITIONAL ANALYSES
1 Stratify the population into 4 groups according to the total transfusion requirement
1 patients receiving 10 units or less of any blood product 24 hrs or 11-15 units 48 hrsvs
2 patients receiving 11-15 units of any blood product 24 hrs or 16-20 units 48 hrs vs
3 patients receiving 16-20 units of any blood product 24 hrs or 21-25 units 48 hrs vs
4 patients receiving more than 20 units of any blood product 24 hrs or more than 25 units 48 hrs
2 Outcome predicted by a joint function general interaction of total plasma transfusion and total blood cell transfusion will be assessed in an exploratory way by inspection and by agnostic modelling in the mold of Multivariate Adaptive Regression Splines MARS and recursive partitioning ie Classification And Regression Trees CART
3 Redefine intervention and control group as 4th and 1st quartile of FFPRBC ratio Initially the population will be divide into 4 groups according to quartiles and compared the population below 1st quartile with the population above the 4th quartile which will define the low vs the high FFP group resp However to allow for stratification for operation type ruptured AAA vs intact AAA vs occlusive disease it may be necessary to adjust the percentile cut to retain power in the analyses For instance the population may be cut according to tertiles or if there is sufficient data cut by quintiles 5 groups or deciles 10 groups
4 Confine the population to patient with blood loss above 50 of total blood volume calculated by Naddlers equation accounting for sex weight and height If height and weight are not available the registered blood loss must exceed 2 L in females and 25 L in males
5 Adjusting exclusively for calendar year sex age Charlsons comorbidity index score and center ie excluding priority and antithrombotic therapy
MISSING DATA
Missing data will not be an issue for the number of blood transfusions because units of blood products transfused are used as an inclusion criterion All remaining covariates are discrete and missing data for each of those will be included as separate parameters factor level
STATISTICAL SIGNIFICANCE LEVEL
Bonferroni adjustment of the significance level will be applied to control for multiple testing
With one primary and four secondary outcomes only a P-value below 001 0055 will be considered statistically significant A P-value between 001 and 005 will be considered borderline significant
The primary analysis will be a stratified cox regression model
STRATIFICATION
type of surgerycondition ruptured AAA vs intact AAA vs aorto-iliac occlusive disease source DVR
sex CPR
Center Rigshospitalet vs Gentofte vs Slagelse vs Odense vs Kolding vs Aarhus vs Viborg vs Aalborg source DVR
COVARIATE ADJUSTMENT
calendar time DVR
age CPR
Carlsons comorbidity index score DNPR
Priority Acute vs Sub-acute vs Elective source DVR
Use of anti-thrombotic drugs DPDB A covariate of 4 levels ATC code is noted in parenthesis
1 None vs
2 Anti-platelet therapy
acetylsalicylic acid B01AC06 or
dipyridamole B01AC07 eg persantin or asasantin
3 Anti-platelet therapy thienopyridines-like drugs
clopidogrel B01AC04 or
ticagrelor B01AC24 eg Brilique or
prasugrel B01AC22 eg Efient Comment patients prescribed thienopyridines in combination with aspirin will be included in this thienopyridine anti-platelet group 3
4 Anti-coagulant therapy
Vitamin K antagonists B01AA eg warfarin or phenprocoumon
Low-molecular weight heparine B01AB01-10
Direct thrombin inhibitors B01AE eg PradaxaDabigatran
Direct factor Xa inhibitors B01AF eg RivaroxabanXarelto Comment patients prescribed both anticoagulant- and antiplatelet therapy and will be included in this Anti-coagulant group 4
ADDITIONAL ANALYSES
1 Stratify the population into 4 groups according to the total transfusion requirement
1 patients receiving 10 units or less of any blood product 24 hrs or 11-15 units 48 hrsvs
2 patients receiving 11-15 units of any blood product 24 hrs or 16-20 units 48 hrs vs
3 patients receiving 16-20 units of any blood product 24 hrs or 21-25 units 48 hrs vs
4 patients receiving more than 20 units of any blood product 24 hrs or more than 25 units 48 hrs
2 Outcome predicted by a joint function general interaction of total plasma transfusion and total blood cell transfusion will be assessed in an exploratory way by inspection and by agnostic modelling in the mold of Multivariate Adaptive Regression Splines MARS and recursive partitioning ie Classification And Regression Trees CART
3 Redefine intervention and control group as 4th and 1st quartile of FFPRBC ratio Initially the population will be divide into 4 groups according to quartiles and compared the population below 1st quartile with the population above the 4th quartile which will define the low vs the high FFP group resp However to allow for stratification for operation type ruptured AAA vs intact AAA vs occlusive disease it may be necessary to adjust the percentile cut to retain power in the analyses For instance the population may be cut according to tertiles or if there is sufficient data cut by quintiles 5 groups or deciles 10 groups
4 Confine the population to patient with blood loss above 50 of total blood volume calculated by Naddlers equation accounting for sex weight and height If height and weight are not available the registered blood loss must exceed 2 L in females and 25 L in males
5 Adjusting exclusively for calendar year sex age Charlsons comorbidity index score and center ie excluding priority and antithrombotic therapy
MISSING DATA
Missing data will not be an issue for the number of blood transfusions because units of blood products transfused are used as an inclusion criterion All remaining covariates are discrete and missing data for each of those will be included as separate parameters factor level
STATISTICAL SIGNIFICANCE LEVEL
Bonferroni adjustment of the significance level will be applied to control for multiple testing
With one primary and four secondary outcomes only a P-value below 001 0055 will be considered statistically significant A P-value between 001 and 005 will be considered borderline significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None