Does Caffeine Reduce Postoperative Bowel Paralysis After Elective Colectomy? (CaCo)
Primary Purpose
Postoperative Ileus, Laparoscopic Colectomy Without Stoma Formation, Colorectal Neoplasm
Status
Terminated
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Caffeine (100 mg)
Caffeine (200 mg)
corn starch (250 mg approx.)
Radiopaque marker
Sponsored by
About this trial
This is an interventional prevention trial for Postoperative Ileus focused on measuring colectomy, laparoscopy, caffeine
Eligibility Criteria
Inclusion Criteria:
- Patients scheduled for elective laparoscopic colectomy (right or left hemicolectomy, segmental resection, extended hemicolectomy, sigmoid resection, upper rectum (anastomosis higher than 7 cm ab ano))
- There will be no upper age limit. If elderly patients are considered fit for surgery, they will be included in the study.
- Informed consent
- Application of epidural analgesia
Exclusion Criteria:
- Participation in another concurrent interventional trial
- Need for a stoma (colostomy or ileostomy) or reversal of a stoma, if the patient had a complete bowel obstruction
- Known hypersensitivity or allergy to caffeine/coffee
- Expected lack of compliance
- American Society of Anesthesiologists (ASA) Physical Status Score of IV or V
- Impaired mental state or language problems
- Alcoholism or drug abuse
- Previous extensive abdominal surgery
- Inflammatory bowel disease
- Clinically significant cardiac arrhythmia
- Cardiac insufficiency
- Pregnancy, lactation, or childbearing potential without using adequate contraception
- Intake of opioid analgesics, or steroids >5mg/d for ≥7 days before surgery
- Under anti-depressive medication
- Liver cirrhosis or compromised liver function (MELD score >15)
- Emergency procedure
Sites / Locations
- Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen
- Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Caffeine (100 mg)
Caffeine (200 mg)
corn starch (250 mg approx.)
Arm Description
Verum 1 with 100 mg caffeine
Verum 2 with 200 mg caffeine
approx. 250 mg corn starch as placebo
Outcomes
Primary Outcome Measures
Time to first bowel movement
Time from end of surgery (time of closing suture) until patient's first bowel movement (passage of stool) in hours.
A patient is considered to have met the primary endpoint when he or she had first tolerated food (recovery of upper GI function) and experienced a bowel movement for the first time (recovery of lower GI function).
Secondary Outcome Measures
Time to first flatus
Time from end of surgery until patient's first flatus in hours. The passage of flatus will be determined by questioning the patient; the passage of a bowel movement will be determined by reference to nursing records or by the clinical judgment of the investigator or designee following questioning the patient.
Time to tolerance of solid food
Time from end of surgery until patient tolerates intake of solid food in hours. Tolerance of food is defined as the first time the patient is able to eat solid food (any food re-quiring chewing) without vomiting or significant nausea within 4 h after the meal, and without reversion to only enteral fluids.
Postoperative vomiting events
Number of times patient has to vomit.
Colonic passage time
On day 1, 2 and 3 after surgery patients take one capsule with radioopaque markers. On day 4 location and count of markers is determined by X-ray imaging and the colonic passage time is determined (Metcalf 1987).
Actual postoperative hospital stay
Number of days from surgery until actual discharge.
Theoretical postoperative hospital stay
Days from surgery until patient would be fit for release. Often patients stay longer in hospital than clinically required. Thus, evaluation of theoretical hospital stay.
A patient is fit for release if:
there had been bowel movement
solid food is tolerated
no serious pain
unproblematic mobilisation
surgical wound shows no sign of inflammation, or wound can be treated well in an outpatient setting
normal inflammatory markers (≤135 mg/l C-reactive protein (CRP), ≤9 10⁹/l white blood cell count)
Daily doses of analgetics
Amount, type, and time of application of analgetics will be obtained from medical and nursing records.
Postoperative pain
evaluated on the numeric rating scale (0 - 10, steps of 1)
Postoperative mobilization
Scoring:
0: 24 h in bed
1: Out of bed only to go to bathroom
2: Out of bed on free will
Overall fluid intake
all fluids in ml per day
Blood pressure
3 times daily
Pulse
3 times daily (or more often if required)
Intensive care
number of days in intensive care unit
Well-being
well-being evaluating on day 2 and 4 after surgery using the Basle mental state scale as well as 5 additional items to evaluate the effects of caffeine. (Hobi 1985, Hobi 1989)
Sleep behaviour
Leeds Sleep Evaluation Questionnaire (LSEQ) on day 2 and 4 after surgery. (Parrott 1986)
Sleeping habits
Questionnaire evaluating duration and deepness of sleep.
Satisfaction with surgery
Questionnaire on day 4 about satisfaction of treatment
Consumption of sleep inducing drugs
amount and type of sleep inducing drugs
Full Information
NCT ID
NCT02510911
First Posted
July 27, 2015
Last Updated
August 3, 2021
Sponsor
Thomas Steffen
Collaborators
Gottfried und Julia Bangerter-Rhyner Foundation, Switzerland
1. Study Identification
Unique Protocol Identification Number
NCT02510911
Brief Title
Does Caffeine Reduce Postoperative Bowel Paralysis After Elective Colectomy?
Acronym
CaCo
Official Title
Does Caffeine Reduce Postoperative Bowel Paralysis After Elective Colectomy? - A Randomized, Placebo-controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
lack of effect at interims analysis
Study Start Date
August 2015 (undefined)
Primary Completion Date
August 2020 (Actual)
Study Completion Date
December 22, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Thomas Steffen
Collaborators
Gottfried und Julia Bangerter-Rhyner Foundation, Switzerland
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Postoperative bowel paralysis is common after abdominal operations, including colectomy. As a result, hospitalization may be prolonged leading to increased cost. A recent randomized controlled trial from the University of Heidelberg showed that consumption of regular black coffee after colectomy is safe and associated with a significantly faster resumption of intestinal motility (Müller 2012). The mechanism how coffee stimulates intestinal motility is unknown but caffeine seems to be the most likely stimulating agent.
Thus, this trial addresses the question: Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy?
Patients after laparoscopic colectomy will receive either 100 mg caffeine, 200 mg caffeine, or 250mg corn starch (placebo) 3 times daily in identically looking gelatin capsules.
The study is a randomized, controlled trial, with blinding of physicians, patients and nursing stuff (evaluating the endpoints).
Primary endpoint will be the time to first bowel movement.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Ileus, Laparoscopic Colectomy Without Stoma Formation, Colorectal Neoplasm, Diverticulitis
Keywords
colectomy, laparoscopy, caffeine
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Caffeine (100 mg)
Arm Type
Experimental
Arm Description
Verum 1 with 100 mg caffeine
Arm Title
Caffeine (200 mg)
Arm Type
Experimental
Arm Description
Verum 2 with 200 mg caffeine
Arm Title
corn starch (250 mg approx.)
Arm Type
Placebo Comparator
Arm Description
approx. 250 mg corn starch as placebo
Intervention Type
Drug
Intervention Name(s)
Caffeine (100 mg)
Other Intervention Name(s)
coffeinum, methyltheobromine, 1,3,7-trimethyl-3,7-dihydro-1H-purin-2,4-dion, CAS No: 56-08-2, Ph.Eur: 6.0/027, ATC code: N06BC01
Intervention Description
Patients after laparoscopic colectomy will receive 3 times daily capsules with 100 mg caffeine together with the meals.
First capsule will be taken on the evening of surgery if surgery was completed before 1 pm, otherwise the first capsule will be taken on the morning of the next day.
Treatment consists of 10 capsules and will be stopped after the first solid bowel movement.
Intervention Type
Drug
Intervention Name(s)
Caffeine (200 mg)
Other Intervention Name(s)
coffeinum, methyltheobromine, 1,3,7-trimethyl-3,7-dihydro-1H-purin-2,4-dion, CAS No: 56-08-2, Ph.Eur: 6.0/027, ATC code: N06BC01
Intervention Description
Patients after laparoscopic colectomy will receive 3 times daily capsules with 200 mg caffeine together with the meals.
First capsule will be taken on the evening of surgery if surgery was completed before 1 pm, otherwise the first capsule will be taken on the morning of the next day.
Treatment consists of 10 capsules and will be stopped after the first solid bowel movement.
Intervention Type
Drug
Intervention Name(s)
corn starch (250 mg approx.)
Other Intervention Name(s)
Amylum maydis
Intervention Description
Patients after laparoscopic colectomy will receive 3 times daily capsules with 250 mg corn starch together with the meals.
First capsule will be taken on the evening of surgery if surgery was completed before 1 pm, otherwise the first capsule will be taken on the morning of the next day.
Treatment consists of 10 capsules and will be stopped after the first solid bowel movement.
Intervention Type
Other
Intervention Name(s)
Radiopaque marker
Other Intervention Name(s)
Colon Transit, PZN 3351272, GTIN Code 7629999004153
Intervention Description
On the morning of the first, second and third day after surgery patients will take 1 capsule each day with radiopaque markers .
On day 4 after surgery an abdominal X-ray will be performed to localize the markers.
Each gelatin capsule contains 10 markers consisting of polyurethane encapsulated barium sulfate (40%).
Primary Outcome Measure Information:
Title
Time to first bowel movement
Description
Time from end of surgery (time of closing suture) until patient's first bowel movement (passage of stool) in hours.
A patient is considered to have met the primary endpoint when he or she had first tolerated food (recovery of upper GI function) and experienced a bowel movement for the first time (recovery of lower GI function).
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Time to first flatus
Description
Time from end of surgery until patient's first flatus in hours. The passage of flatus will be determined by questioning the patient; the passage of a bowel movement will be determined by reference to nursing records or by the clinical judgment of the investigator or designee following questioning the patient.
Time Frame
7 days
Title
Time to tolerance of solid food
Description
Time from end of surgery until patient tolerates intake of solid food in hours. Tolerance of food is defined as the first time the patient is able to eat solid food (any food re-quiring chewing) without vomiting or significant nausea within 4 h after the meal, and without reversion to only enteral fluids.
Time Frame
7 days
Title
Postoperative vomiting events
Description
Number of times patient has to vomit.
Time Frame
7 days
Title
Colonic passage time
Description
On day 1, 2 and 3 after surgery patients take one capsule with radioopaque markers. On day 4 location and count of markers is determined by X-ray imaging and the colonic passage time is determined (Metcalf 1987).
Time Frame
4 days
Title
Actual postoperative hospital stay
Description
Number of days from surgery until actual discharge.
Time Frame
30 days
Title
Theoretical postoperative hospital stay
Description
Days from surgery until patient would be fit for release. Often patients stay longer in hospital than clinically required. Thus, evaluation of theoretical hospital stay.
A patient is fit for release if:
there had been bowel movement
solid food is tolerated
no serious pain
unproblematic mobilisation
surgical wound shows no sign of inflammation, or wound can be treated well in an outpatient setting
normal inflammatory markers (≤135 mg/l C-reactive protein (CRP), ≤9 10⁹/l white blood cell count)
Time Frame
30 days
Title
Daily doses of analgetics
Description
Amount, type, and time of application of analgetics will be obtained from medical and nursing records.
Time Frame
30 days
Title
Postoperative pain
Description
evaluated on the numeric rating scale (0 - 10, steps of 1)
Time Frame
7 days
Title
Postoperative mobilization
Description
Scoring:
0: 24 h in bed
1: Out of bed only to go to bathroom
2: Out of bed on free will
Time Frame
7 days
Title
Overall fluid intake
Description
all fluids in ml per day
Time Frame
7 days
Title
Blood pressure
Description
3 times daily
Time Frame
7 days
Title
Pulse
Description
3 times daily (or more often if required)
Time Frame
7 days
Title
Intensive care
Description
number of days in intensive care unit
Time Frame
14 days
Title
Well-being
Description
well-being evaluating on day 2 and 4 after surgery using the Basle mental state scale as well as 5 additional items to evaluate the effects of caffeine. (Hobi 1985, Hobi 1989)
Time Frame
4 days
Title
Sleep behaviour
Description
Leeds Sleep Evaluation Questionnaire (LSEQ) on day 2 and 4 after surgery. (Parrott 1986)
Time Frame
4 days
Title
Sleeping habits
Description
Questionnaire evaluating duration and deepness of sleep.
Time Frame
4 days
Title
Satisfaction with surgery
Description
Questionnaire on day 4 about satisfaction of treatment
Time Frame
4 days
Title
Consumption of sleep inducing drugs
Description
amount and type of sleep inducing drugs
Time Frame
7 days
Other Pre-specified Outcome Measures:
Title
preoperative caffeine consumption
Description
Questionnaire evaluation the caffeine consumption of patients (type of beverages, amount etc)
Time Frame
before surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients scheduled for elective laparoscopic colectomy (right or left hemicolectomy, segmental resection, extended hemicolectomy, sigmoid resection, upper rectum (anastomosis higher than 7 cm ab ano))
There will be no upper age limit. If elderly patients are considered fit for surgery, they will be included in the study.
Informed consent
Application of epidural analgesia
Exclusion Criteria:
Participation in another concurrent interventional trial
Need for a stoma (colostomy or ileostomy) or reversal of a stoma, if the patient had a complete bowel obstruction
Known hypersensitivity or allergy to caffeine/coffee
Expected lack of compliance
American Society of Anesthesiologists (ASA) Physical Status Score of IV or V
Impaired mental state or language problems
Alcoholism or drug abuse
Previous extensive abdominal surgery
Inflammatory bowel disease
Clinically significant cardiac arrhythmia
Cardiac insufficiency
Pregnancy, lactation, or childbearing potential without using adequate contraception
Intake of opioid analgesics, or steroids >5mg/d for ≥7 days before surgery
Under anti-depressive medication
Liver cirrhosis or compromised liver function (MELD score >15)
Emergency procedure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Steffen, MD
Organizational Affiliation
Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen
City
Rorschach
ZIP/Postal Code
9400
Country
Switzerland
Facility Name
Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22987303
Citation
Muller SA, Rahbari NN, Schneider F, Warschkow R, Simon T, von Frankenberg M, Bork U, Weitz J, Schmied BM, Buchler MW. Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy. Br J Surg. 2012 Nov;99(11):1530-8. doi: 10.1002/bjs.8885. Epub 2012 Sep 14.
Results Reference
background
PubMed Identifier
3023168
Citation
Metcalf AM, Phillips SF, Zinsmeister AR, MacCarty RL, Beart RW, Wolff BG. Simplified assessment of segmental colonic transit. Gastroenterology. 1987 Jan;92(1):40-7. doi: 10.1016/0016-5085(87)90837-7.
Results Reference
background
PubMed Identifier
2928619
Citation
Hobi V, Gerhard U, Gutzwiller F. [A report on experiences using Goldberg's GHQ (General Health Questionnaire)]. Schweiz Rundsch Med Prax. 1989 Feb 28;78(9):219-25. German.
Results Reference
background
Citation
Hobi V. Basler Befindlichkeits-Skala. Ein Self-Rating zur Verlaufsmessung der Befindlichkeit. Manual. 1 ed. Weinheim: Beltz Test GmbH, 1985.
Results Reference
background
PubMed Identifier
6777817
Citation
Parrott AC, Hindmarch I. The Leeds Sleep Evaluation Questionnaire in psychopharmacological investigations - a review. Psychopharmacology (Berl). 1980;71(2):173-9. doi: 10.1007/BF00434408.
Results Reference
background
PubMed Identifier
35909263
Citation
Abbassi F, Muller SA, Steffen T, Schmied BM, Warschkow R, Beutner U, Tarantino I. Caffeine for intestinal transit after laparoscopic colectomy: randomized clinical trial (CaCo trial). Br J Surg. 2022 Nov 22;109(12):1216-1223. doi: 10.1093/bjs/znac265.
Results Reference
derived
PubMed Identifier
27044596
Citation
Kruse C, Muller SA, Warschkow R, Luthi C, Brunner W, Marti L, Sulz MC, Schmied BM, Tarantino I, Beutner U. Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy? (CaCo trial): study protocol for a randomized controlled trial. Trials. 2016 Apr 4;17:186. doi: 10.1186/s13063-016-1297-1.
Results Reference
derived
Links:
URL
http://www.chirurgie.kssg.ch/
Description
Web site of the Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen (German only)
Learn more about this trial
Does Caffeine Reduce Postoperative Bowel Paralysis After Elective Colectomy?
We'll reach out to this number within 24 hrs