Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03757455 |
| Other study ID # |
R18125 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2020 |
| Est. completion date |
October 1, 2021 |
Study information
| Verified date |
November 2021 |
| Source |
Tampere University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In the study, the enhanced recovery after surgery (ERAS) program is applied to total
pancreatectomy (TP) and low-risk pancreaticoduodenectomy (PD) patients identified by a small
number of acinar cells in the cut edge of the pancreas. The research setting is randomized
and controlled. All patients arriving at the Tampere University Hospital (TAUH) for PD or TP
surgery are recruited into the study. Recruited patients are randomized to the ERAS protocol
and to the standard protocol recovery program. The ERAS program differs from the normal care
protocol preoperatively, intraoperatively and postoperatively as explained in the following
section.
In the ERAS protocol, both on the previous day of the surgery and on the following days, the
patient is discussed with the patient about the benefits of the protocol used and the
recovery program objectives. The purpose is to motivate and encourage the patient. On the day
of surgery, the patient's intake of food and fluids is allowed to be closer to the surgery
and the patient is also given a carbohydrate drink two hours before surgery. The nasogastric
tube set at the beginning of surgery is removed at the end of the surgery and peripancreatic
or perihepatic drains are not routinely placed. After surgery, drinking is allowed after four
hours and the patient is encouraged to move as actively as possible in the bed. On the first
and second postoperative day, the patient is allowed to enjoy normal food and drink according
to his or her ability, and pancreatic capsules are given in the course of food. Additionally,
the analgesic to be administered through the epidural cannula is dosed as far as possible to
allow mobilization of the patient. The discussion on the benefits and recovery targets of the
ERAS protocol are continued. On the third postoperative day, the epidural infusion is
discontinued and the pain medication is moved to opioid-based pain management. This is
continued until specific criteria for passing to the follow-up care are met.
Typical complications (pancreatic fistula, delayed gastric emptying, postpancreatectomy
hemorrhage) are registered during hospitalization and their severity ratings according to
ISGPS, ISPGF and Clavien-Dindo classifications are also determined. Other variables
registered are the number of intensive care days, situations requiring new surgeries, 30 and
90 day mortality, the completion time of the criteria for passing to follow up care, and the
total length of hospitalization. In addition, the need for readmissions is registered. The
implementation of the ERAS protocol is followed by a separate tracking template, in which the
nurses record the progress of the goals specified in the protocol on a daily basis. The
results of the study are analyzed with the intention-to-treat principle.
Description:
In the study, the enhanced recovery after surgery (ERAS) program is applied to total
pancreatectomy (TP) and low-risk pancreaticoduodenectomy (PD) patients identified by a small
number of acinar cells in the cut edge of the pancreas. The research setting is randomized
and controlled. All patients arriving at the Tampere University Hospital (TAUH) for PD or TP
surgery are recruited into the study. Patients will be sent a handout of the study along with
the letter of invitation for the surgery itself. Recruitment takes place at the first
appointment of the surgery where the surgeon presents the study to the patient. If the
patient wishes to participate in the study, the patient issues a signature on the consent
form. They are randomized to this ERAS program for shortened recovery period and a standard
protocol recovery program. Allocation to the groups takes place using opaque envelope-coded
randomization codes. The research nurse prepares the envelopes in twelve patient
randomization blocs.
To determine the low risk PD-patients recruited, the pathologial sample of the cut-edge of
the pancreas is analyzed by pathologist during the surgery. If the pancreatic cut-edge
contains less than 40% acinar cells, the patients is considered low risk patient. This method
is based on earlier studies in our pancreatic research group. All TP patients are per se in
the small complication risk group. Only those patients with a low risk of complications
continue to be involved in the study in standardized or ERAS protocol groups according to the
original allocation.
ERAS protocol consist of following actions in comparison to standard protocol:
First appointment:
- Enlightenment on the benefits and objectives of the ERAS protocol
Call to the patient day before the surgery:
- Discussing the course, benefits and goals of care in ERAS
- 4 dl PreOp drink before bedtime
Operation day:
- Fluid intake allowed 2 hours before surgery
- 2 dl PreOP drink 2 h before cutting
Intraoperative:
- Drains in the peripancreatic or perihepatic regions are not set unless the surgeon sees
this particular reason
- The nasogastric tube is removed at the end of the surgery
Postoperative:
- Mobilization with nurses assisted, possibly sitting on the edge of the bed if possible
- Drinks allowed after 4h surgery
Postoperative day 1:
- Drinking and normal food by mouth according to the patient's capabilities
- Removal of urinary catheter
- Intravenous liquids only if needed
- Mobilization physiotherapist and nurse guided as actively as possible
- Pain management by epidural cannula at the level to make mobilization possible
- Discussion of the ERAS protocol (objectives, benefits, time of passing to follow up
care) (also continues on the following days) and encouragement
- If drains are set: amylase tests
- Pancreatin capsules per os before eating, 25,000 IU 1-2 capsules on big meals and 1 on
snack (continued on the following days)
Postoperative day 2:
- Mobilization: As much as possible, autonomous movement
Postoperative day 3:
- Ending epidural infusion, cannula removal later if p.o. medication is sufficient
- As independent as possible
Pain relief: oxycodone / naloxone p.o. to keep mobilization possible:
1. 2x 5 / 2.5 mg ≤ 60 kg
2. 2x 10/5 mg> 60 kg
3. 2x 15 / 7.5> 100kg. In addition, paracetamol 1g three times a day p.o.
Postoperative day 4:
- Support and encouragement continues
- Pain management at a level that allows mobility
- Passing to follow up care when following criteria are met:
1. The patient should be able to enjoy at least two meals without significant nausea
2. Bowel movements returned
3. The patient should be able to move, urinate, and perform daily operations at
pre-operative level
4. The patient does not need strong analgesics when moving
5. The temperature, pulse rate, blood pressure and respiratory rate should be in the
reference range or pre-cut level.
6. The patient has no signs of bleeding.
- Pain medication changes to tramadol 100 mg three times a day when discharged
For all those involved in the study, PD's surgery technique is standardized to classic
Whipple surgery, submersion bowel-pancreatic seam, antecholic gastro-jejunostomy and
entero-entero anastomosis.
The patient is left out of the study if a patient is undergoing another surgery than PD, TP
or does not undergo surgery at all. Likewise, the study is suspended from the consideration
of the surgeon if, for any other reason, the patient may be expected to be a high
complication risk patient.
Typical complications (pancreatic fistula, delayed gastric emptying, postpancreatectomy
hemorrhage) are registered during hospitalization and their severity ratings according to
ISGPS, ISPGF and Clavien-Dindo classifications are also determined. Other variables
registered are the number of intensive care days, situations requiring new surgeries, 30 and
90 day mortality, the completion time of the criteria for passing to follow up care, and the
total length of hospitalization. In addition, the need for readmissions is registered. The
implementation of the ERAS protocol is followed by a separate tracking template, in which the
nurses record the progress of the goals specified in the protocol on a daily basis. The
results of the study are analyzed with the intention-to-treat principle.
The main variable of the study is the treatment period at the university hospital. The side
variables are the total treatment time, the total amount of complications, and the number of
readmissions. The hypothesis is that recovery is faster in the ERAS group, but the occurrence
of complications and readmissions are the same in both groups.
A statistical power calculation, assuming 80% statistical power (1-β) and 5% significance
level (α), was carried out with a continuous outcome superiority trial. The sample size was
calculated using the main coefficient of variation assuming that in the standard protocolled
patients the median of the discharge time is nine days and in the ERAS program for seven
days, i.e. a presumption of approximately 20% decrease in treatment days. Three days were
assumed to be the standard deviation. The sample size thus obtained is 36 per group, which is
rounded up to approximately 80 patients in total.
When evaluating the time spent collecting the data, it is assumed that 20% of the patients
will drop out of the study for various reasons. In TAUH, approximately 100 PDs and 15 TP
patients are operated in two years and approximately 70% of patients of PD are in a low risk
of complications. Consequently, the number of patients to be collected in two years would be
approximately 0.7 ∙ 0.8 ∙ 100 + 0.8 ∙ 15 ≈ 68, which is almost sufficient for the purpose of
this study to achieve statistical significance. The estimated duration of the study is
therefore little more than two years. However, the study will be continued as long as
necessary to collect the required number of patients. When half of the final number of
patients has been collected, an interim analysis is made of the differences in the groups. If
the results of the ERAS protocol are at least as good as the standard group, the study will
be continued.
All recruited patients are asked for written consent for participation in the study. The
research file is stored in the TAUH research register. Patient information and research
results are treated confidentially in the manner required by the Finnish Personal Data Act.
The final research results are reported at group level and the identification of individual
investigators is not possible. The research funding is provided by the Tampereen Pancreatic
Research Group the largest funders being the State Research Fund and Sigrid Jusélius
Foundation. Also Finnish Medicine Foundation in providing personal funding.
The research has been approved by the Ethics Committee of the Tampere University Hospital.
The earlier ERAS studies have shown that their use is safe and in most cases beneficial to
the patient. In this study, it is novel that only small complication risk patients are
included in the study. In addition, halfway between the research is performed an interim
analysis to ensure the safety of the ERAS protocol. Patient's own consent is asked before
surgery, and information on the research is provided within the limits of the success of the
study. Patient's refusal or suspension of study does not affect the patient's treatment in
any way.
