View source for Okabayashi et al. (2020): L-Carnitine Improves Postoperative Liver Function in Hepatectomized Patients

{{Reference
|Reference=Publication: L-Carnitine Improves Postoperative Liver Function in Hepatectomized Patients
}}

=Brief summary=
In this study, patients who had their liver removed due to liver cancer or biliary tract disease were included. The patients were randomly divided into 2 groups, with one group receiving carnitine for 2 weeks, while the other group received no additional intervention. After the surgery, a slightly shorter hospital stay was observed for the patients who received carnitine. No significant differences were found regarding postoperative complications or the frequency of liver failure. The authors provide little information about the study procedure, leaving some methodological questions unanswered.


In dieser Studie wurden Patienten eingeschlossen, denen die Leber aufgrund einer Leberkrebs- oder Gallenwegserkrankung entfernt wurde. Die Patienten wurden zufällig in 2 Gruppen eingeteilt, wovon eine Gruppe über 2 Wochen Carnitin erhielt und die andere Gruppe erhielt keine zusätzliche Maßnahme. Nach der OP zeigte sich ein leicht kürzerer Krankenhausaufenthalt für die Patienten, die Carnitin erhielten. In Hinsicht auf Komplikationen nach der OP oder der Häufigkeit des Leberversagens konnten keine bedeutsamen Unterschiede gefunden werden. Die Autoren geben wenig Informationen über den Ablauf der Studie, so dass einige methodische Fragen offenbleiben.

=Study Design=

{{Study Design (RCT)
|Perspective=Prospective
|Centralized=Monocentric
|Blinding=No
|Is randomized=Yes
|Cross-over=No
|Number of arms=2
}}
=Study characteristics=

{{RCT study general properties
|Inclusion criteria=Preoperative contrast-enhanced computed tomography was available within 30 days of the scheduled surgery.
Criteria for hepatectomy included:
* Absence or controllability of ascites.
* Serum total bilirubin level ≤2 mg/dL (no patients required diuretics for ascites)
|Exclusion criteria=* Previous liver surgery.
* Body weight loss >10% during the 6 months before surgery.
* Presence of distant metastases.
* Seriously impaired function of vital organs due to respiratory, renal, or heart disease.
* Biliary cancer, due to the need for biliary resection, bilioenteric anastomosis, and lymphadenectomy during hepatectomy for this condition.
|N randomized=208
|Analysis=ITT Analysis
|Specifications on analyses=ITT analysis not specified, but no drop-out occured.
|Countries of data collection=Japan
|LoE=Level 2 Oxford 2011
|Outcome timeline=Baseline: 2 weeks before surgery 
T1: After surgery
}}
=Characteristics of participants=

{{Characteristics of participants
|Setting=Curative
|Types of cancer=Gastrointestinal Cancers - Liver Cancer
|Stage cancer=NI
|Cancer stage specification=NI
|Comorbidity=Comorbidity with hepatitis B (n=73), hepatitis C (n=104), alcohol (n=95), and non-alcoholic steatohepatitis (n=24)
|Current cancer therapy=Surgery
|Specifications on cancer therapies=Hepatectomy (n=30 bisegmentectomy or extended hepatectomy, n=69 segmentectomy, and n=109 subsegmentectomy)
|Previous cancer therapies=NI
|Gender=Mixed
|Gender specifications=Intervention arm 67%, control arm 67.6% male
|Age groups=Adults (18+)
|Age groups specification=Age (mean ± SD): intervention arm 73 ± 9.8 years, control arm 73 ± 10.7 years
}}
=Arms=

{{Arm
|Arm type=Intervention
|Number of participants (arm)=102
|Drop-out=0
|Drop-out reasons=NA
|Intervention=L-Carnitine
|Dosage and regime=Oral, 30 mg/kg body weight for 2 weeks before surgery
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=Authors: “L-carnitine was well tolerated by all patients.”

No differences in mortality as of March 2018.
|Order number=1
|Arm topic=Carnitine
}}
{{Arm
|Arm type=Passive control
|Number of participants (arm)=106
|Drop-out=0
|Drop-out reasons=NA
|Intervention=No further intervention
|Dosage and regime=NA
|One-time application=No
|Duration in days=14
|Side Effects / Interactions=Authors: “L-carnitine was well tolerated by all patients.”

No differences in mortality as of March 2018.
|Order number=2
|Arm topic=Carnitine
}}
{{Arm Overview}}
=Outcomes=

{{Outcome
|Outcome type=Primary
|Outcome name=Postoperative morbidity/ complications
|Outcome specification=Classification according to Clavien-Dindo, 50-50 criteria (Prothrombin time < 50% and bilirubin level > 50 µmol/L on the 3rd and 5th postoperative days are associated with an increased risk of postoperative mortality), posthepatic liver failure (PHLF)
|Type of measurement=Blood Test
|Results during intervention=After Surgery: 
* No significant differences between the intervention arm and the control arm in the frequency of postoperative complications, including bile leakage, pleural effusion, respiratory insufficiency, perihepatic abscess, and postoperative ileus.
* Classification according to Clavien-Dindo: Morbidity was 10.4% in the control arm and 6.9% in the intervention arm; 7 patients (6%) in the control arm and 3 patients (3%) in the intervention arm had at least one severe complication (Grade III-V), with no significant difference between the groups.
* 50-50 criteria: 6 patients (6%) in the control arm and 2 patients (2%) in the intervention arm, with no significant difference between the groups.
* PHLF: 12 patients (11%) in the control arm and 6 patients (6%) in the intervention arm, with no significant difference between the groups.
|Results after intervention=NA
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=1
|Outcome topic=Carnitine
}}
{{Outcome
|Outcome type=Primary
|Outcome name=Length of hospital stay
|Outcome specification=NA
|Type of measurement=Observation
|Results during intervention=Slightly significant shorter stay in the intervention arm compared to the control arm: Median stay was 12 days (range, 5-144 days) in the control arm and 10 days (range, 7-157 days) in the intervention arm, p=0.048. The length of stay in the intensive care unit was 1 day (range, 0-1 days) in both arms.
|Results after intervention=NA
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=2
|Outcome topic=Carnitine
}}
{{Outcome
|Outcome type=Primary
|Outcome name=Mortality rate
|Outcome specification=NA
|Type of measurement=Observation
|Results during intervention=NI
|Results after intervention=One death occurred 62 days post-operation in the control arm (segmentectomy) due to bleeding from esophageal varices 2 weeks after surgery, followed by multi-organ failure. No other surgical mortalities or readmissions related to the surgery were reported.
|Bias arising from the randomization process=?
|Bias due to deviation from intended intervention (assignment to intervention)=?
|Bias due to deviation from intended intervention (adhering to intervention)=NA
|Bias due to missing outcome data=?
|Bias in measurement of the outcome=?
|Bias in selection of the reported result=?
|Other sources of bias=?
|Overall RoB judgment=?
|Order number=3
|Outcome topic=Carnitine
}}
{{Outcome Overview}}
=Funding and Conflicts of Interest=

{{Funding and Conflicts of Interest
|Funding=This work was supported by grants from the K ¯ochi Organi-zation for Medical Reformation and Renewal. Dr. TakehiroOkabayashi is the guarantor of this work, had full access to allthe data in the study, and takes responsibility for the integrityof the data and the accuracy of the data analysis.
|Conflicts of Interest=According to authors no conflict of interest.
}}
=Further points for assessing the study=

{{Further points for assessing the study
|power analysis performed=?
|Sample size corresponds to power analysis=?
|Reasons given for samples being too small according to power analysis=?
|Samples sufficiently large=?
|Ethnicity mentioned=?
|Other explanations for an effect besides the investigated intervention=?
|Possibility of attention effects=?
|Possibility of placebo effects=?
|Other reasons=?
|Correct use of parametric and non-parametric tests=?
|Correction for multiple testing=?
|Measurement of compliance=?
|Consistent reporting in numbers=?
|Comprehensive and coherent reporting=?
|Cross-over=?
|sufficient washout period=?
|Tested for carry-over effects=?
|Were sequence effects tested=?
|Effect sizes reported=?
|Were side effects systematically recorded=?
|Side effects taken into account in the interpretation of the results=?
|Ethics / CoI / Funding=?
|Blinding reliable=?
|Check whether blinding was successful=?
}}
{{Additional Notes
|Additional Notes=PRO:
* Ethical approval obtained.
* Large sample size.
* Study registered.
* Baseline comparison conducted.
* Power analysis performed.

CONTRA:
* No description of the randomization process.
* Financial support was initially not disclosed, but later indicated.
* Open design.
* PHLF: Table in article shows n=5 in the control arm, but text reports n=6.
* No information on the treatment of the control group.
* No control for multiple testing.
}}