| Figure 1. Study flow diagram. |
| Figure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. |
| Figure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study. |
| Figure 4. Trial sequential analysis of mortality (selective bowel decontamination versus inactive control)The diversity-adjusted required information size (DARIS) was calculated to 9753 participants, based on the proportion of participants in the control group with the outcome of 6.8%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue line). After accruing 190 participants in three trials, only 1.95% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional boundaries (dotted red line) have also not been crossed by the cumulative Z-curve. |
| Figure 5. Trial sequential analysis of mortality (prebiotics with probiotics versus prebiotics)The diversity-adjusted required information size (DARIS) was calculated to 9753 participants, based on the proportion of participants in the control group with the outcome of 6.8%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue line). After accruing 129 participants in two trials, only 1.32% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional boundaries (dotted red line) have also not been crossed by the cumulative Z-curve. |
| Figure 6. Trial sequential analysis of retransplantation (selective bowel decontamination versus inactive control)The diversity-adjusted required information size (DARIS) was calculated to 8086 participants, based on the proportion of participants in the control group with the outcome of 8.1%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue line). After accruing 132 participants in two trials, only 1.63% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional boundaries (dotted red line) have also not been crossed by the cumulative Z-curve. |
| Figure 7. Trial sequential analysis of mortality (prebiotics with probiotics versus prebiotics)The diversity-adjusted required information size (DARIS) was calculated to 46,458 participants, based on the proportion of participants in the control group with the outcome of 1.5%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue line). After accruing 129 participants in two trials, only 0.28% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional boundaries (dotted red line) have also not been crossed by the cumulative Z-curve. |
| Figure 8. Trial sequential analysis of infection (selective bowel decontamination versus inactive control)The diversity-adjusted required information size (DARIS) was calculated to 2639 participants, based on the proportion of participants in the control group with the outcome of 44.9%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing 256 participants in four trials, only 9.7% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the futility area. The cumulative Z-curve (blue line) does not cross the trial sequential monitoring boundaries (continuous red line) or the conventional boundaries (dotted red line). |
| Figure 9. Trial sequential analysis of infection (prebiotics with probiotics versus prebiotics)The diversity-adjusted required information size (DARIS) was calculated to 3745 participants, based on the proportion of participants in the control group with the outcome of 41.5%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 71.51%. After accruing 129 participants in two trials, only 3.44% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional boundaries (dotted red line) have not been crossed by the cumulative Z-curve (blue line) after two trials although the conventional boundary was crossed favouring probiotics with prebiotics after the first trial. |
| Figure 10. Trial sequential analysis of intensive therapy unit stay (prebiotics with probiotics versus prebiotics)The diversity-adjusted required information size (DARIS) was 8005 participants based on a minimal relevant difference (MIRD) of 1 day, a variance (VAR) of 254.96, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D^{2}) of 0%. After accruing 129 participants in two trials, only 1.61% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional boundaries (dotted red line) have not been crossed by the cumulative Z-curve (blue line). |
| Figure 11. Trial sequential analysis of hospital stay (prebiotics with probiotics versus prebiotics)The diversity-adjusted required information size (DARIS) was 11,621 participants based on a minimal relevant difference (MIRD) of 1 day, a variance (VAR) of 370.14, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D^{2}) of 0%. After accruing 129 participants in two trials, only 1.11% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional boundaries (dotted red line) have not been crossed by the cumulative Z-curve (blue line). |
| Analysis 1.1. Comparison 1 Intervention versus control, Outcome 1 Mortality. |
| Analysis 1.2. Comparison 1 Intervention versus control, Outcome 2 Retransplantation. |
| Analysis 1.3. Comparison 1 Intervention versus control, Outcome 3 Graft rejection requiring medical treatment. |
| Analysis 1.4. Comparison 1 Intervention versus control, Outcome 4 Graft rejection unspecified treatment. |
| Analysis 1.5. Comparison 1 Intervention versus control, Outcome 5 Proportion of participants with infections. |
| Analysis 1.6. Comparison 1 Intervention versus control, Outcome 6 Number of infection episodes. |
| Analysis 1.7. Comparison 1 Intervention versus control, Outcome 7 Intensive therapy unit stay. |
| Analysis 1.8. Comparison 1 Intervention versus control, Outcome 8 Hospital stay. |