Aim of the PRECious trial is to evaluate the effect of a standardized postoperative algorithm for quality control (via standardized measurement of CRP levels and CT-scan imaging) on morbidity and mortality after major digestive surgery.
ID
Source
Brief title
Condition
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Mortality; during 12 month follow-up
2. Morbidity associated with major complications and/or after reoperation
within 12 months after index operation, including:
o Fistula after reoperation; connection between two hollow-organs and/or skin;
entero-cutaneous, entero-vesical and entero-vaginal fistula.
o Wound dehiscence/incisional hernia/open abdomen after reoperation;
full-thickness discontinuity in abdominal wall with bulging of abdominal
contents, with or without obstruction.
o Bowel obstruction or herniation after major complication; Due to adhesions,
diagnosis to be confirmed in CT or surgery.
o Abscess; pus-containing non pre-existent cavity, requiring percutaneous
drainage or surgery. Confirmed by gram-stain or culture.
o Abdominal compartment syndrome after reoperation: intra-abdominal
hypertension > 25 mmHg (modified Burch criteria) with tense abdomen and with
increasing respiratory and/or renal failure. Measured by the urinary bladder
pressure method.
o Perforation of visceral organ after major complication and confirmed at
surgery
o Unplanned enterostomy upon reoperation
o Enterostomy dysfunction due to prolapse, stenosis or retraction.
o Myocardial infarction: electrocardiogram and enzyme changes suggestive of
myocardial infarction and/or admission to coronary care unit
o Pulmonary embolus; confirmed on ventilation perfusion scan or CTa-scan
o Respiratory insufficiency due to pneumonia, pleural effusion or pulmonary
edema; necessitating mechanical ventilation.
o Cerebrovascular accident; ischemic or non-ischemic with persistent paresis or
paralysis without previous history
o Renal failure; urine production<500 ml/24h with rising levels of blood urea
nitrogen and creatinin, combined with dehydration; necessitating any form of
dialysis
o Urosepsis; urinary tract infection with positive urine and blood cultures and
circulatory shock.
o Upper GI bleeding requiring endoscopic treatment or embolization therapy
o Intra-abdominal bleeding; surgical bleeding after relaparotomy or hematoma
requiring surgical evacuation.
o Anastomotic leak after relaparotomy requiring precutaneous drainage or
reoperation
Secondary outcome
Secondary outcome measures are:
* Quality of Life as measured by; EQ-5D 5L Questionnaire
* Add-on value of CRP (only measured during intervention period): Grading of
patient by physician in charge during morning visits, before CRP levels are
measured, on a scale of 0 -10 (zero being healthy patient, ten being a patient
at risk of acute death).
* Duration of admission
* Duration of intensive care admission
* Cost-efficiency
Background summary
In major digestive surgery, defined als all gastrointestinal resections with
reconstruction via anastomosis or ostomy, major postoperative complications are
observed in up to 20% of patients. These complications necessitate invasive
treatment such as reoperation, percutaneous drainage and intensive care
admission and are associated with increased morbidity and mortality, which in
turn leads to longer lengths of hospital and intensive care stay, unplanned
procedures, increased risk of cancer recurrence and higher costs.
Current time to diagnosis of major complications is approximately 8 days. A
delay in diagnosis is associated with a further increase in morbidity and
mortality. Early diagnosis and treatment decreases morbidity and mortality, but
is challenging since with clinical, serological and even imaging techniques the
difference between a complications and physiological postoperative response can
be hard to distinguish. Furthermore, clinical assessment showed a low
predictive value for anastomotic leakage. This further supports the need for a
standardized quality control algorithm after major abdominal surgery. At the
moment no such standardized algorithm exists.
C-reactive protein (CRP) is a known marker of infection and inflammation. This
acute phase protein is synthesized in the liver after stimulation by cytokines.
CRP is elevated after surgery. a peak is observed 48-72 hours postoperatively.
Half-life of CRP is approximately 19 hours and independent of diet, diurnal
rhythm and organ function. Due to these characteristics CRP is considered a
valuable marker for inflammation.
Several studies have assessed the use of CRP as a marker for postoperative
complications, with promising results. Based on our own systematic review and
pooled-analysis of 1427 patients we established an optimal cut-off of 140 mg/L
on postoperative day 3,4 and 5, with a sensitivity of 81,7% and specificity of
61,6%.
CRP is however non-specific for location, thus additional imaging is required.
Computed Tomography scan imaging (CT-scan) is the current imaging modality of
choice. In our database of 399 patients CT-scan imaging showed a sensitivity of
91,7% and specificity of 100% for diagnosis of major complications, this is
confirmed in recent literature.
In 2008 Den Dulk et al. implemented a standardized scoring system for the
clinical status of patients after colorectal surgery. With this system they
managed to decrease the time between index operation and diagnosis of
anastomotic leakage from 8 to 6 days. Furthermore, mortality decreased from 39%
to 24% (p=0,24). This study further supports the need for a standardized
quality control algorithm after major digestive surgery, however the optimal
algorithm is yet to be established. CRP and CT-scan imaging adequately aid
diagnosis of postoperative complications, however currently their use is only
on demand. The PRECious protocol is a standardized postoperative algorithm
aimed at quality control and early diagnosis and treatment of major
complications.
Study objective
Aim of the PRECious trial is to evaluate the effect of a standardized
postoperative algorithm for quality control (via standardized measurement of
CRP levels and CT-scan imaging) on morbidity and mortality after major
digestive surgery.
Study design
The PRECious trial is performed based on a stepped-wedge design, it is a
multi-center study. In the first phase of the trial all patients will be
allocated to the control group (n=350). These patients receive standard
postoperative care and standard CRP measurements on postoparative day 3,4 and
5, for observational purposes.
After an implementational phase of one month, all patients will be allocated to
the intervention group (n=350). Patients allocated to this group will receive
postoperative monitoring according to the PRECious protocol, which entails
standardised measurements of CRP on postoperative day 3,4 and 5. If CRP levels
exceed 140 mg/L on postoperative day 3,4 or 5, additional CT-scan imaging of
the operated area will be performed.
Intervention
Standard postoperative monitoring, which includes only "on demand" additional
laboratory testing is compared to the PRECious protocol. The PRECious protocol
entails standardized CRP measurements on postoperative day 3,4 and 5. If CRP
levels exceed 140 mg/L, additional CT-scan imaging will be performed to
diagnose or exclude major complications.
Study burden and risks
The PRECious trial aims to establish the effect of standardised postoperative
quality control on postoperative morbidity and mortality associated with major
complications.
Risks and burden associated with participation in the study are believed to be
low. In the intervention group patients are subjected to three venous
punctures, which can be complicated by formation of a hematoma, dizziness and
collaps. These complications are all transient.
If measured CRP levels exceed 140 mg/L additional CT-scan imaging is performed.
Risks of CT-scan imaging consist of radiation risks. As stated above, the risks
due to radiation are believed to be low and are surpassed by the morbidity and
mortality asscoated with delays in diagnosis of complications. Other possible
complications are mainly associated with the contrast materials, hence patients
with known allergies for contrast are not included in the study. Similarly
patients with decreased (GFR < 30 ml/min/1,73 m2) renal function are not
included and renal function is monitored in all patients undergoing CT-scan
imaging.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Patient older than 18 years of age
Patients planned for elective Major Abdominal Surgery
Informed consent
Exclusion criteria
Patients undergoing acute major abdominal surgery
ASA (American Society of Anaesthesiologists) classification of 4 or higher
Insufficient dutch language skills
Contrast allergies
glomerular filtration rate (GFR)of less than 30 ml/min/1,73m2 or patients with
multiple myeloma
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02102217 |
| CCMO | NL43534.029.15 |