Does Caffeine Reduce Postoperative Bowel Paralysis After Elective Colectomy?

Study Overview
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Brief Summary
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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.

Official Title
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Does Caffeine Reduce Postoperative Bowel Paralysis After Elective Colectomy? - A Randomized, Placebo-controlled Trial

Conditions
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Postoperative Ileus, Laparoscopic Colectomy Without Stoma Formation, Colorectal Neoplasm, Diverticulitis

Intervention / Treatment
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* Drug: Caffeine (100 mg)
* Drug: Caffeine (200 mg)
* Drug: corn starch (250 mg approx.)
* Other: Radiopaque marker


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caffeine (100 mg)<br>Verum 1 with 100 mg caffeine | Drug: Caffeine (100 mg)<br>* 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.<br>* Other names: ATC code: N06BC01;Other: Radiopaque marker<br>* 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%).<br>* Other names: GTIN Code 7629999004153;|
| Experimental: Caffeine (200 mg)<br>Verum 2 with 200 mg caffeine | Drug: Caffeine (200 mg)<br>* 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.<br>* Other names: ATC code: N06BC01;Other: Radiopaque marker<br>* 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%).<br>* Other names: GTIN Code 7629999004153;|
| Placebo Comparator: corn starch (250 mg approx.)<br>approx. 250 mg corn starch as placebo | Drug: corn starch (250 mg approx.)<br>* 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.<br>* Other names: Amylum maydis;Other: Radiopaque marker<br>* 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%).<br>* Other names: GTIN Code 7629999004153;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 7 days | 
| 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. | 7 days | 
| Postoperative vomiting events | Number of times patient has to vomit. | 7 days | 
| 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). | 4 days | 
| Actual postoperative hospital stay | Number of days from surgery until actual discharge. | 30 days | 
| 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) | 30 days | 
| Daily doses of analgetics | Amount, type, and time of application of analgetics will be obtained from medical and nursing records. | 30 days | 
| Postoperative pain | evaluated on the numeric rating scale (0 - 10, steps of 1) | 7 days | 
| Postoperative mobilization | Scoring: 0: 24 h in bed 1: Out of bed only to go to bathroom 2: Out of bed on free will | 7 days | 
| Overall fluid intake | all fluids in ml per day | 7 days | 
| Blood pressure | 3 times daily | 7 days | 
| Pulse | 3 times daily (or more often if required) | 7 days | 
| Intensive care | number of days in intensive care unit | 14 days | 
| 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) | 4 days | 
| Sleep behaviour | Leeds Sleep Evaluation Questionnaire (LSEQ) on day 2 and 4 after surgery. (Parrott 1986) | 4 days | 
| Sleeping habits | Questionnaire evaluating duration and deepness of sleep. | 4 days | 
| Satisfaction with surgery | Questionnaire on day 4 about satisfaction of treatment | 4 days | 
| Consumption of sleep inducing drugs | amount and type of sleep inducing drugs | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colectomy, laparoscopy, caffeine