Studying the effect of the the Squill-Oxymel on patients with occupational obstructive pulmonary disease: A Pilot Randomized Triple-Blinded Placebo-Controlled Clinical Trial

To evaluate the effects of Squill Oxymel on pulmonary function, respiratory symptoms, and treatment tolerability in patients with occupational obstructive lung diseases compared with placebo

A randomized, placebo controlled clinical trial with a two by two factorial design, individual block randomization, and planned blinding of participants, investigators, and outcome assessors. A total of 144 participants will be equally allocated to four groups of 36

The study will be conducted in Semnan, Iran, among workers with occupational obstructive lung diseases. Eligible participants will receive the assigned intervention for 60 days. Pulmonary function and respiratory symptoms will be assessed at baseline, day 30, and day 60. Coded study products will maintain blinding to active treatment or placebo

Workers aged 18 to 65 years with at least one year of occupational exposure to respiratory hazards, chronic respiratory symptoms, and spirometric evidence of airflow obstruction will be included. Exclusion criteria include nonobstructive pulmonary diseases, severe cardiovascular diseases, smoking history exceeding 20 pack years, recent respiratory infections, pregnancy, and breastfeeding

Group A receives Squill Oxymel plus standard treatment; Group B receives placebo plus standard treatment; Group C receives Squill Oxymel without standard treatment; Group D receives placebo without standard treatment. The intervention duration is 60 days

Changes in forced expiratory volume in one second (FEV1); forced vital capacity (FVC); FEV1/FVC ratio; forced expiratory flow between 25% and 75% of FVC (FEF25–75); peak inspiratory flow (PIF)

In this study, individual-level block randomization will be used to allocate eligible participants to the study groups. After assessment of the inclusion and exclusion criteria and obtaining written informed consent, participants will be randomly assigned in a 1:1:1:1 allocation ratio to four groups: Group A (Squill-Oxymel plus standard treatment), Group B (placebo plus standard treatment), Group C (Squill-Oxymel without standard treatment), and Group D (placebo without standard treatment). It is proposed that the random allocation sequence be generated using statistical software with randomly varying block sizes of 4 and 8 by an independent researcher who is not involved in participant recruitment, clinical assessment, or outcome evaluation. Within each block, participants will be randomly allocated to the four study groups to maintain balanced group sizes while minimizing the predictability of subsequent assignments. No stratification is proposed. To ensure allocation concealment, it is proposed that the randomization sequence be maintained by an independent researcher using sequentially numbered, opaque, sealed envelopes. Each envelope will be opened only after confirmation of eligibility, completion of baseline assessments, and formal enrollment of the participant. Allocation codes will remain confidential until completion of the study and data analysis, except when emergency unblinding is necessary to ensure participant safety.

In this study, blinding will be implemented to minimize potential bias during intervention administration and outcome assessment. Three categories, including participants, the investigator, and outcome assessors, will be blinded to the allocation of Squill-Oxymel or placebo. Squill-Oxymel syrup and placebo will be prepared to be as similar as possible in color, taste, odor, consistency, volume, and packaging. The study products will be labeled with unique identification codes without indicating whether they contain the active intervention or placebo. Product coding will be performed by an independent individual who is not involved in the research procedures. The confidential code list will be securely maintained until completion of the study. Participants will be informed about their participation in the clinical trial and the possibility of receiving either Squill-Oxymel or placebo, but they will remain unaware of the assigned product. The investigator responsible for conducting the study and the outcome assessors will not have access to the treatment allocation codes. Pulmonary function outcomes, including FEV1, FVC, FEV1/FVC, FEF25–75, and PIF, will be assessed at baseline, day 30, and day 60 without the outcome assessors being informed of the assigned study product. Clinical care providers responsible for prescribing or supervising standard treatment may not be blinded to the standard-treatment component of group allocation if they are aware of whether participants receive standard treatment. Adverse events and clinical conditions will be monitored and documented throughout the study. Emergency unblinding will be permitted when knowledge of the assigned study product is essential for appropriate clinical management of a serious adverse event.

Deidentified individual participant data collected during the clinical trial, including demographic characteristics, pulmonary function measurements, respiratory symptoms, treatment allocation, and adverse events, as well as the study protocol and data collection forms. All personal identifiers will be removed before sharing.

Data and supporting documents will be available beginning six months after publication of the main study results and will remain accessible for five years thereafter, subject to applicable ethical and institutional requirements.

Qualified researchers affiliated with universities, academic institutions, research centers, or healthcare organizations may request access to the data and supporting documents for legitimate scientific purposes.

Data may be used for scientific research, secondary analyses, systematic reviews, and meta analyses. Applicants must submit a research proposal describing the intended use of the data. Access will be subject to approval by the principal investigator and applicable ethics requirements. Attempts to identify participants, unauthorized redistribution, and commercial use without permission are prohibited.

Data access requests should be submitted by email to the research team at Semnan University of Medical Sciences, Semnan, Iran. Contact person: Sobhan Sangesari Email: sobhansangesari@gmail.com Requests will be forwarded to the principal investigator for review and approval.

Applicants must submit a written request specifying their institutional affiliation, research objectives, and intended analyses. The research team will review the request and assess ethical compliance. A decision will normally be communicated within 30 days of receiving a complete application. Following approval and completion of any required data sharing agreement, the requested documents or deidentified data will be provided through a secure electronic method within 15 working days.