The PRIMROSE Trial (PRIMROSE)

A Randomised Controlled Trial to Evaluate the Impact of Thoracic PRehabilitation With Inspiratory Muscle tRaining cOmpared to Standard prEhabilitation in People With Lung Cancer for Surgical Treatment . The PRIMROSE Trial

Smoking is a major cause for developing lung cancer. People diagnosed with lung cancer, may be offered surgery which offers a complete cure. Smoking also damages the lungs and compromises a person's lung function, resulting in shortness of breath. Breathlessness limits the ability to carry out daily physical activities and exercise and makes people vulnerable to developing post procedure complications and even death. Some people with surgically treatable lung cancer have a poor ability to exercise and compromised lung function and are not fit for surgery. They will instead be referred for radiation therapy, chemotherapy or palliative care. Surgery is the preferred treatment option.

The pulmonary rehabilitation program (Prehab) improves fitness levels. In addition, it improves the level of breathlessness, exercise capacity and vulnerability of people with lung cancer, with the aim of making them fit for safe surgery. By adding a breathing training device to the Prehab program, the investigators aim to further improve participants fitness for surgery, lower their risk of developing complications and the time spent in hospital after the procedure. The breathing training device is called an inspiratory muscle training device. The hand-held device helps to train and strengthen the breathing muscles, which are then able to work more effectively. After the procedure, participants may be able to breathe and exercise more easily reducing their risk of developing complications and improving outcomes.

The study will compare two groups of people with lung cancer having surgical removal of part of the lung, at a specialist hospital . One group will receive standard Prehab and inspiratory muscle training with the device prior to the procedure; patients in the second group with receive standard Prehab prior to the procedure. Participants will be followed up for twelve months.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Lung Resection; Inspiratory Muscle Training; Prehabilitation; Respiratory Complications; Length of Hospital Stay
• Intervention / Treatment: Device: Inspiratory muscle training (POWERBreathe); Other: Standard Prehab

Detailed Description

To compare inspiratory muscle training (IMT) with standard Prehabilitation (Prehab) to Prehab alone, in people with lung cancer for surgical procedure.

One hundred and thirty-four participants will be recruited for the study (67 for each arm) and with an anticipated attrition rate of 20-25%, one hundred participants will finally be studied.

All adults with lung cancer, aged18 years or over, diagnosed or suspected of non-small cell lung cancer (NSCLC) with surgically resectable disease, who are referred for pre-treatment optimization with Prehab from the lung cancer Multi-Disciplinary Teams (MDTs).

Adults with lung cancer are referred for pre-treatment optimization with Prehab if they meet the following referral criteria: ≥1 Medical Research Council (MRC) dyspnoea score; or ≥1 World Health Organization (WHO) performance status (PS); age ≥ 70 years or frailty index >3; borderline or poor pulmonary function (forced expiratory volume in one second (FEV1) or diffusion capacity for carbon monoxide (DLCO) <50%); sedentary people despite having adequate FEV1 or DLCO. People will be included in the trial if they are capable of giving consent to participation and aged 18 and over.

Additionally, people who have no contraindications to IMT use.

The aim is to evaluate the impact of thoracic Prehab with IMT compared to standard Prehab in reducing post procedural pulmonary complications following surgical resection in people with lung cancer in a randomised control trial.

Descriptive statistics will be used to summarise participants' characteristics and outcome measures. Statistical analyses will be performed using SPSS statistical software, version 20.0 (IBM Corporation, Armonk, NY, USA). Two-sided significance tests will be used (a\0.05). Data will be presented as mean and standard deviation (SD), or median and interquartile range (IQR) for variables with a skewed distribution. Differences between groups in categorical variables will be tested with Chi square or Fisher's exact test. For continuous data the student's t test or the Mann-Whitney U test will be used. The Wilcoxon signed rank test will be used to compare MIP and QoL at T0 and T1 and T2. Relative risk will be calculated for post procedural pulmonary complications (PPCs) graded 1-V using the Clavien Dindo classification and impact of IMT on the study group compared to the control group. Assuming a 36.7 incidence of PPC after the procedure in the control arm and using a significance level of 0.05 and a power of 80%, 50 participants are required in each arm.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ira Goldsmith, Professor; Phone Number: 44 01792 704084; Email: Ira.Goldsmith@wales.nhs.uk
• Study Contact Backup: Name: Tracy Jones, Physiotherapy; Phone Number: 23670 44 01792 702222; Email: tracy.jones6@wales.nhs.uk

Study Locations

• United Kingdom
  • Swansea, United Kingdom, SA6 6NL
    • Recruiting
    • Swansea Bay University Health Board
    • Contact: Tracy Jones, Physiotherapy; Phone Number: 23670 01792 702222; Email: tracy.jones6@wales.nhs.uk
    • Principal Investigator: Tracy Jones

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Adults with lung cancer with surgically resectable disease who are referred for pre-treatment optimization with Prehab, from the lung cancer Multi-Disciplinary Teams (MDTs).

The referral criteria for Prehab is below:

• ≥1 Medical Research Council (MRC) dyspnoea score
• ≥1 World Health Organization (WHO) performance status (PS)
• Age ≥ 70 years
• Frailty index >3
• Borderline or poor pulmonary function (forced expiratory volume in one second (FEV1) < 50% or diffusion capacity for carbon monoxide (DLCO) <50%)
• Sedentary people despite having adequate FEV1 or DLCO
• People who are eligible for surgical procedures, including endobronchial excision of tumour, or lobectomy, segmental resection, pneumonectomy or wedge resection, either via a minimally invasive approach or a standard thoracotomy approach

Additionally:

• Participants will be included in the trial if they are capable of providing verbal and written consent for Prehab, and written consent for undergoing a surgical procedure for lung cancer
• People over 18 years of age
• All people will be considered regardless of their baseline respiratory muscle strength

Exclusion Criteria: Inclusion criteria not met

• People diagnosed with other cancers namely, metastatic lung cancer, mesothelioma, sarcoma, mediastinal tumours, or benign diseases
• People who decline Prehab
• People who do not consent to Prehab, and do not attend Prehab. People who do not consent to surgery
• People with a high cardiovascular risk for Prehab and awaiting investigations or interventions (including unstable angina and syncope)
• People with a serious concomitant disorder that would compromise safety during Prehab
• People with an abdominal hernia or recent abdominal surgery
• People with a history of spontaneous pneumothorax and/or evidence of large bullae on radiological imaging
• People with an inability to understand written and/or spoken English (only if carers are able to translate)
• People with a perforated ear drum
• People with worsening heart failure signs and symptoms after IMT
• People with pulmonary hypertension
• People who have suffered from or likely to suffer from costochondritis
• If a participant was involved in a similar study, with potential to cause bias or conflict of interest then they will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prehab plus device; Standard Prehab plus inspiratory muscle training device	Device: Inspiratory muscle training (POWERBreathe); Resistance training for inspiratory muscles prior to procedure.; Other: Standard Prehab; Physical optimisation
Active Comparator: Prehab; Standard Prehab	Other: Standard Prehab; Physical optimisation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post procedure complications	Post procedure complications following surgical resection in people with lung cancer. This will be graded I-V using the Clavien Dindo Classification. Post procedure complications will be broadly classified as minor (grade 1) and major complications (grade 2-5 where 5 is death). The investigators want to learn from this study, whether an inspiratory muscle trainer helps reduce grade 2 post procedure complications to grade 1 or no complications, and thereby help shorten the length of stay in hospital for people undergoing lung resection surgery. Lower numbers mean a better outcome. Higher numbers mean a worse outcome.	On hospital discharge (assessed up to 2 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Quality of Life	European Organisation for Research and Treatment of Cancer (EORTC) questionnaire (EOTRC QLQ-30). The scores are transformed into a 0-100 range, where 0 is the lowest possible score and 100 is the highest. A higher score indicates a better outcome for functional and global health scores. However, a higher score on the symptom sales represent a greater burden of symptoms and a worse outcome.	At Prehab initial assessment, periprocedural, at hospital discharge (assessed up to 2 months), 1 month post procedure and 3 months post procedure.
Dyspnoea Score	Medical research council (MRC) dyspnoea score. This scale is measured from 0 to 4. A higher score means worse outcomes. A lower score means better outcomes.	At Prehab initial assessment, every two weeks whilst undergoing Prehab, periprocedural, at hospital discharge (assessed up to 2 months) and 1 month post procedure.
Performance Status	World Health Organization (WHO) performance status. This assigns scores from 0 to 5. A higher score indicates worse outcomes and a lower score indicates better outcomes.	At Prehab initial assessment, every two weeks whilst undergoing Prehab, periprocedural, at hospital discharge (assessed up to 2 months), 1 month post procedure.
Thoracoscore	The Thoracic Surgery Scoring System is used in thoracic procedures to estimate mortality risk. It calculates risk based on the person co-morbidities and procedure. The Thoracoscore ranges from -7.37 to 7.37. A higher score indicates a potential worse outcome/ more risk. A lower score indicates a potential better outcome/ less risk.	At prehab initial assessment and periprocedural.
Frailty Index	The Clinical Frailty Index is a tool used to assess a persons health status, by measuring the accumulation of health deficits. The scale is 1 to 9. A higher score indicates a greater level frailty and a lower score indicates a lower level of frailty. A higher score is associated with a worse outcome.	At Prehab assessment, every two weeks whilst undergoing Prehab, periprocedural, at hospital discharge (assessed up to 2 months) and 1 month post procedure.
Levels of activity	Categorised as sedentary, lightly active, moderately active and very active.	On Prehab initial assessment, every two weeks of Prehab, periprocedural, at hospital discharge (assessed up to 2 months) and 1 month post procedure.
Maximum Inspiratory Pressure (MIP)	Measure of respiratory muscle strength. The higher the number the stronger the respiratory muscles are. For healthy adults, normal ranges are 100 to 120cmH20 for men and 70 to 80 cmH20 in women.	At Prehab initial assessment, periprocedural and at hospital discharge (assessed up to 2 months).
Forced expiratory volume in 1 second (FEV1)	The amount of air a person can forcefully exhale in the first second after a deep breath. Ranges are categorized by percentage of predicted range. In normal lung function, 80% or higher is expected. In mild airflow obstruction values ranges vary between 50-79% and severe airflow obstruction ranges between 30-49% and very severe impairment below 30%.	At Prehab initial assessment
Transfer factor for carbon monoxide (TLCO)	Measures the amount of carbon monoxide (CO) transferred per minute from alveolar gas to red blood cells (RBCs). This is considered normal when 76% to 140% of the predicted value is achieved. Mild, moderate and severe ranges are for values below 76%.	At Prehab initial assessment
Mortality	Death rate	At hospital discharge (assessed up to 2 months), 1 month post procedure , 3 months post procedure and 1 year post procedure
Length of hospital admission	The numbers of days the participant spent in hospital. A lower number indicates a better outcome. A higher number indicates a worse outcome.	On hospital discharge (assessed up to 2 months).

Collaborators and Investigators

• Sponsor: Swansea Bay University Health Board
• Investigators: Study Director: Lisa Wakeman, Swansea Bay University Health Board

Publications and helpful links

Helpful Links

• Link to power breathe website - the inspiratory muscle training device to be used as part of the study

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 12, 2025
• First Submitted That Met QC Criteria: January 15, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Inspiratory muscle training; Prehabilitation; Lung surgery; length of hospital stay; Lung resection; Randomised control trial
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: PRIMROSE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will be confidential and study results will be disseminated collectively on completion

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No