Protocol

 

Version 1.2:

Download the Protocol (PDF)

 

Version 1.1:

Download the Protocol (PDF)

 

Historique des modifications du protocol:

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 intervention’s effect (or lack thereof).

Approved 24.09.2025

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