Bärthel 2012.

Study characteristics
Methods	Randomised, open label, pilot clinical trial Country: Germany Single centre Period of recruitment: September 2006 to October 2008 Number randomised: 80 (1:1) Postrandomisation dropouts: 5 (6.25%). 2 from the prostaglandin group and 3 from the control group Lost to follow‐up: not reported Inclusion criteria: adults undergoing liver transplantation Exclusion criteria: living‐related and split‐liver transplants, retransplantations, known intolerance to the study medication, severe circulatory instability after graft reperfusion with prolonged noradrenaline dosage ≥ 0.5 μg/kg bodyweight/minute.
Participants	Experimental: 40 (29 men and 11 women) Control: 40 (30 men and 10 women) Mean age (years): 54 Women: 21 (26.3%)
Interventions	Experimental: prostaglandin I2 analogue, iloprost, administered immediately after admission to intensive care unit by continuous intravenous infusion at a rate of 1 ng/kg bodyweight/minute for 7 days Control: standard care with no added intervention All participants were treated with a comparable calcineurin inhibitor‐based quadruple induction immunosuppressive regimen.
Outcomes	Primary outcome Incidence of primary graft dysfunction or initial non‐function within 7 days after liver transplantation (experimental group: 2 participants and control group: 8 participants); 4 participants in the control group underwent liver retransplantation; 2 participants in the experimental group required liver retransplantation Note: trial authors changed the definition of graft dysfunction in a post hoc analysis. Secondary outcomes Participant survival – mortality reported at 30 days, and within 6 months after lung transplantation (5 participants in the experimental group and 3 participants in the control group) Length of intensive care unit and overall hospital stay Requirement of blood‐coagulating substances within 7 days after liver transplantation However, the authors reported on more outcomes, such as biliary complications (in 8 participants in the experimental and 8 participants in the control group). Complications in the prostaglandin group included: respiratory insufficiency 6; pleural effusion 8; acute renal failure 5; pneumonia 4; peritonitis 2; sepsis/multiple organ failure 2; opportunistic (i.e. cytomegalovirus) 6; cardiac 2; gastrointestinal tract 5; relaparotomy 9; wound healing impairment 3; new‐onset cancer 1 Complications in the control group included: blood/lymphatic 2; respiratory insufficiency 7; pleural effusion 3; acute renal failure 8; pneumonia 3; urinary tract 2; peritonitis 1; sepsis/multiple organ failure 2; opportunistic (i.e. cytomegalovirus) 6; cardiac 3; gastrointestinal tract 6; relaparotomy 8; wound healing impairment 2 Follow‐up (months): 6
Notes	Source of funding: not reported Trial name/trial registry number: not reported Quote: "The procedures abide by Good Clinical Practice and the ethical principles described in the current (at that time) revision of Declaration of Helsinki." Emailed erik.baerthel@med.uni‐jena.de in May 2019, December 2020, and March 2022. Received no reply It is unclear if all the authors of publication participated in the trial as information was lacking.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible participants were randomised (1:1) in blocks of 2 up to 6 participants to the iloprost or control group using a random allocation software.
Allocation concealment (selection bias)	Unclear risk	No mention of allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open label.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Primary end points were mainly observer‐reported outcomes not involving judgement.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcomes of all randomised participants provided.
Selective reporting (reporting bias)	Unclear risk	The study protocol was not available. There was insufficient information to judge this domain.
Other bias	Unclear risk	Baseline imbalance present as the authors stated "… higher proportion of patients with severe liver dysfunction in the treatment group." Higher proportion of extended criteria donors (which are donors with certain risk factors such as donor age, steatosis, donation after cardiac death, and donors with increased risk of disease transmission) in the control group. It is unclear whether trial was stopped early or not because sample size calculation was performed based on feasibility. Quote: "A sample size of 80 patients was chosen for reasons of feasibility for the pilot study to prove the treatment concept and to obtain preliminary estimates of the treatment effect." Intention‐to‐treat analysis and per‐protocol analyses were performed.