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Accepted for/Published in: JMIR Research Protocols

Date Submitted: May 4, 2025
Date Accepted: Dec 18, 2025

The final, peer-reviewed published version of this preprint can be found here:

Efficacy, Safety, and Economic Impact of Cytisinicline Maintenance Therapy in Patients Who Are Candidates for Smoking Cessation: Protocol for a Phase IV, Multicenter, Randomized, Open-Label, Controlled, Parallel Clinical Trial (CITISILONG Trial)

Rabade Castedo C, Estany-Gestal A, Jiménez Ruiz CA, de Granda-Orive JI, Riesco-Miranda JA, Cristóbal Fernández MI, Ramos-Pinedo A, Signes-Costa Miñana J, Gorordo-Unzueta MI, Valido-Morales A, Sellarés -Torres J, Cabrera-César E, Frino-García A, Valdés Cuadrado L

Efficacy, Safety, and Economic Impact of Cytisinicline Maintenance Therapy in Patients Who Are Candidates for Smoking Cessation: Protocol for a Phase IV, Multicenter, Randomized, Open-Label, Controlled, Parallel Clinical Trial (CITISILONG Trial)

JMIR Res Protoc 2026;15:e76815

DOI: 10.2196/76815

PMID: 41576369

PMCID: 12881894

Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.

Efficacy, safety and economic impact of citisinicline maintenance therapy in patients who are candidates for smoking cessation. Protocol for a phase IV, multicentre, randomised, open-label, controlled, parallel, multicentre clinical trial. CITISILONG trial

  • Carlos Rabade Castedo; 
  • Ana Estany-Gestal; 
  • Carlos A Jiménez Ruiz; 
  • José Ignacio de Granda-Orive; 
  • Juan Antonio Riesco-Miranda; 
  • María Isabel Cristóbal Fernández; 
  • Angela Ramos-Pinedo; 
  • Jaime Signes-Costa Miñana; 
  • María Inmaculada Gorordo-Unzueta; 
  • Agustin Valido-Morales; 
  • Jacobo Sellarés -Torres; 
  • Eva Cabrera-César; 
  • Alejandro Frino-García; 
  • Luis Valdés Cuadrado

ABSTRACT

Background:

Cytisynicline has proven to be an effective, efficient and safe molecule in smoking cessation. However, the established 25-day regimen could be insufficient in a high percentage of smokers, so it is necessary to study maintained therapies of this drug.

Objective:

To compare the efficacy of the cytisinicline regimen used in routine clinical practice with two maintained regimens of 50 and 75 days, respectively. In addition, the safety and economic impact of each regimen will be determined.

Methods:

A prospective, multicentre, open-label, controlled, parallel, phase IV clinical trial of 402 smoker patients prepared to quit smoking. Participants will be randomised to three groups in a 1:1:1 ratio, to receive cytisynicline in a clinical practice regimen (25 days) or cytisynicline in a maintained regimen (50 and 75 days respectively). The study was conducted in 10 hospitals in Spain

Results:

Recruitment for the trial and patient enrolment will be completed in May 2026. Follow-up of all participants will extend to June 2027.

Conclusions:

In conclusion, this study evaluates the optimisation of cytisinicline in daily clinical practice, increasing the benefits of its pharmaceutical properties without affecting patient safety. Clinical Trial: European Clinical Trials Register with EUDRACT code 2024-518936-36-00.


 Citation

Please cite as:

Rabade Castedo C, Estany-Gestal A, Jiménez Ruiz CA, de Granda-Orive JI, Riesco-Miranda JA, Cristóbal Fernández MI, Ramos-Pinedo A, Signes-Costa Miñana J, Gorordo-Unzueta MI, Valido-Morales A, Sellarés -Torres J, Cabrera-César E, Frino-García A, Valdés Cuadrado L

Efficacy, Safety, and Economic Impact of Cytisinicline Maintenance Therapy in Patients Who Are Candidates for Smoking Cessation: Protocol for a Phase IV, Multicenter, Randomized, Open-Label, Controlled, Parallel Clinical Trial (CITISILONG Trial)

JMIR Res Protoc 2026;15:e76815

DOI: 10.2196/76815

PMID: 41576369

PMCID: 12881894

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