Protocol
Version 1.3:
Version 1.2:
Version 1.1:
Protocol amendment history:
| Protocol version | Protocol date | Description | Changes to prior version | Status | Approval date |
|---|---|---|---|---|---|
| 1.0 | 28.11.2024 | Initial protocol submission to the ethics committee (Ethikkommission Nordwest- und Zentral Schweiz) in November 2024. | Not approved | 19.12.2025 | |
| 1.1 | 06.01.2025 | Adapted version after comments from the ethics committee. This was the finally approved version before the start of recruitment. | -Change of eligibility criteria: Following the recommendation of the ethics committee, we changed the eligibility criteria and excluded pregnant women from the trial. -Clarification on data collection: We specified when RETUNE uses trial specific data collection and when routine cohort data collection. -Clarification on participation in other research projects: RETUNE participants are allowed to participate in other research while RETUNE participation. -Specification on the trial discontinuation: Participants can discontinue intervention product use and will remain in the cohort. -Addition of monitoring plan: The monitoring procedure is outlined in chapter 9 of the revised protocol. |
Approved | 08.01.2025 |
| 1.1 | 06.01.2025 | Addition of a new center, protocol version remains the same. | -Addition of a new center: The Cantonal Hospital St. Gallen and the University Hospital Zurich has been added as a participating center. | Approved | 15.04.2025 |
| 1.1 | 06.01.2025 | Addition of a new center, protocol version remains the same. | -Addition of a new center: The University Hospital Bern has been added as a participating center. | Approved | 07.05.2025 |
| 1.1 | 06.01.2025 | Addition of a new center, protocol version remains the same. | -Addition of a new center: The University Hospital Geneva has been added as a participating center. | Approved | 09.07.2025 |
| 1.1 | 06.01.2025 | Addition of a new center, protocol version remains the same. | -Addition of a new center: The University Hospital Lausanne has been added as a participating center. | Approved | 29.07.2025 |
| 1.2 | 08.08.202 | Adapted version based on accumulated changes over the course of the trial. | -Addition of a new center: The Cantonal Hospital Aarau has been added as a participating center. -Removal of biochemical verification of smoking cessation: The planned biochemical verification of patient-reported smoking abstinence using plasma anabasine as an explanatory endpoint has been removed. -Changes to secondary endpoints: We have added measurement of total cholesterol in addition to HDL- and LDL-cholesterol. We have also removed death from the composite cardiovascular endpoint, as mortality will be captured as a serious adverse event. -Additional methodological details: We have added information on allocation concealment and blinding. -Correction of primary estimand: An error in the definition of the primary estimand has been corrected, and the description improved for clarity. -Statistical analysis updates: We have added details on the conduct of subgroup analyses and the handling of missing data. -Addition of process evaluation: We have included a paragraph describing the planned process evaluation study to better understand potential mechanisms of the interventionās effect (or lack thereof). |
Approved | 24.09.2025 |
| 1.3 | 16.08.2026 | Adapted version based on accumulated changes over the course of the trial. | -Addition of a new center: The Cantonal Hospital Biel/Bienne has been added as a participating center. -Change of product: We will gradually replace the E-cigarette model used up to now by the E-cigarette model āPen Nexi Pro Aspireā. The reason for the change is, that the originally used e-cigarettes are not commercially available in Switzerland anymore. -Changes to outcomes: The description has been improved for clarity. We have added all-cause death to the composite cardiovascular endpoint. -Clarification of primary estimand: The description has been improved for clarity. We have added risk ratio and absolute risk difference to the summary measure. -Clarification of the statistical analysis: The description for the methods used for the per-protocol analysis has been improved for clarity. -Changes to the pre-specified subgroup analysis: We added 5 new subgroup analysis to the list of pre-specified subgroups of interest. |
Approved | 21.09.2026 |