Clinical trial NCT06919185: Short- and Long-term Effects of Robot-assisted Plication in Diaphragmatic Paralysis
Official title: Short- and Long-term Effects of Robot-assisted Plication in Diaphragmatic Paralysis - the Prospective RAPIDLY-study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Diaphragmatic Plication
Diaphragmatic Paralysis
Diaphragmatic Eventration
Keywords: RATS
robot-assisted thoracic surgery
plication
dyspnea
thoracotomy
Lead sponsor: Uppsala County Council, Sweden
Sponsor class: OTHER_GOV
Collaborators: name: Uppsala University
First posted: 2025-04-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with unilateral diaphragmatic paralysis

Brief summary: Diaphragmatic paralysis may lead to severe symptoms such as breathlessness and reduced physical capacity.

Diaphragmatic plication using Robotic-Assisted Thoracic Surgery (RATS) is a minimally invasive surgical technique developed to improve lung function by correcting diaphragmatic elevation.

While its benefits have been reported in retrospective reports, prospective studies are lacking.

This prospective observational cohort study aimsto evaluate the short- and long-term effects of robot-assisted diaphragmatic plication on subjective breathlessness, physical performance, lung function, blood gases, and imaging findings at five Swedish university hospitals: Gothenburg, Linköping, Lund, Umeå, and Uppsala.

Patients will be assessed preoperatively and postoperatively after one to three months and after one and three years.

Detailed description: Assessments

Patient characteristics:

Age, sex, height, and weight will be recorded. Body mass index (BMI) is calculated by dividing a person's weight by their height in meters squared.

Aetiology of diaphragmatic paralysis, relevant co-morbidities and use of long-term oxygen therapy and/or mechanical ventilation will be recorded.

The date for symptom debut, if known, is recorded. Smoking history is defined as current smoker, ex-smoker (smoking history of ≥100 cigarettes and having quit smoking ≥6 months ago), and never smoker (smoking history of \<100 cigarettes). Smoking is quantified by pack-years (the number of packs of cigarettes a person has smoked daily, multiplied by the number of years they have smoked).

Primary outcome:

The patients' exercise capacity will be evaluated using the 6-minute walking distance (6MWD). The patients are asked to walk as far as possible on a flat, straight surface for six minutes, and the total distance walked is measured.

Secondary outcomes:

Questionnaires:

The modified Borg Scale is a tool with a range from 0 to 10 used to measure an individual's perceived level of breathlessness or muscle fatigue during physical activity, where 0 represents no breathlessness, and 10 represents maximal breathlessness.

The modified Medical Research Council (mMRC) dyspnea scale is used to assess the severity of breathlessness. The scale ranges from 0 to 4, with higher scores indicating more significant breathlessness.

The Dyspnea-12 is a questionnaire used to measure the severity and quality of breathlessness in individuals with respiratory or cardiovascular conditions. It assesses dyspnea's physical and emotional aspects, providing a comprehensive picture of how breathlessness affects a person's life. It consists of 12 items, each with a scale range between 0 (no dyspnea) and 3 (severe dyspnea).

The EuroQol-5-dimension (EQ-5D) questionnaire is one of the most widely used tools for assessing health-related quality of life. It includes five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. These dimensions create a descriptive profile that can be converted into a single summary index, where a score of 1.0 indicates perfect health. Additionally, the tool includes a Visual Analog Scale (VAS), ranging from 0 (worst imaginable health) to 100 (best imaginable health), for self-assessment of overall health status.

Spirometry Spirometry will be conducted 15 minutes after bronchodilation (inhalation of 200 µg salbutamol) in both supine and upright positions. Body plethysmography and single-breath Diffusing Capacity in the Lungs for Carbon Monoxide (DLCO) measurement will be performed. Predicted values will be determined using reference equations from the Global Lung Function Initiative (GLI).

One-minute sit-to-stand test (1-MSTST) This test assesses a person's functional exercise capacity by recording the number of full sit-to-stand repetitions completed in 60 seconds.

The Maximal Inspiratory Pressure (MIP) test is a respiratory test that measures the strength of the inspiratory muscles, particularly the diaphragm. By inhaling as forcefully as possible in a handheld device, the maximum negative pressure generated is recorded.

Blood gas analysis A capillary or arterial blood gas analysis obtains the partial pressure of oxýgen and carbon dioxide (PaCO2) in kilo Pascal (kPa) and Base Excess (BE) in mmol/l. Pulse oximetry obtains oxygen saturation.

Chest X-ray Chest X-rays are acquired in full inspiration and expiration in frontal and lateral views. The distance from the most cranial part of the lung to the highest part of the diaphragm in both frontal and side views are measured separately.

Computerised tomography (CT) of Thorax A CT with a standard protocol to identify and quantify lower lobe atelectasis.

Adverse events Operating time, chest-drain duration, length of hospitalisation, per- and postoperative complications such as pain, bleeding and infections, 30-day readmission and 30-days mortality are recorded.

Statistics Descriptive statistics summarise the data, and inferential statistics compare group differences.

Associations with the outcomes will be analysed using multivariable regression models, including linear regression (for continuous outcome variables) and logistic regression (for categorical outcomes). Repeated measurements within individuals will be managed through multilevel, random-effects models.

Power calculation: Based on a standard deviation of 90 meters in the 6-minute walk test (6MWT) among the general population, and considering that the minimal clinically important difference (MCID) is 53 meters, a total of 45 patients is required.

Assessments pre-operatively Demographics Anthropometrics Co-morbidities Questionnaires Physical capacity tests Spirometry MIP Blood gas analysis Chest X-ray CT scan

Assessments 1-3 months post-operatively Anthropometrics Questionnaires Physical capacity tests Spirometry MIP Blood gas analysis Chest X-ray CT scan

Assessments after 1 and 3 years post-operatively Anthropometrics Questionnaires Physical capacity tests Spirometry MIP Blood gas analysis Chest X-ray

Ethical considerations:

Robot-assisted diaphragm plication is performed at several university hospitals in Sweden and abroad. The patients in this study have been clinically approved for this surgery. They are not exposed to any additional risks in this study beyond being examined more thoroughly with surveys and questionnaires, lung function and performance tests, and chest X-rays before and after the surgical procedure. The study is approved by the Swedish Ethical Review Authority, Dnr 2025-01028-01.

Relevance of research:

Robot-assisted plication in diaphragmatic paralysis is a new operative method performed at many thoracic centres worldwide without being scientifically evaluated in prospective studies. This national multicenter study, with a large cohort by international standards and with validated, highly relevant outcome variables, is expected to gain significant attention among thoracic surgeons and pulmonary physicians worldwide.

Eligibility criteria: Inclusion Criteria:

* Patients with symptomatic unilateral diaphragmatic paralysis persisting for ≥1 year
* Patients are scheduled for RATS at thoracic surgery clinics in five Swedish university hospitals (Gothenburg, Linköping, Lund, Umeå, and Uppsala).

Exclusion Criteria:

* Inability to complete forms in Swedish
* Neuromuscular disease as the cause of diaphragmatic paralysis
* Other significant causes of dyspnea
* Impaired physical capacity from other causes than diaphragmatic paralysis.

Primary outcomes:
measure: 6-minute walking distance (6MWD).
timeFrame: From enrollment to end of observation att 3 years.
Secondary outcomes:
measure: The modified Borg Scale
timeFrame: From enrollment to end of observation att 3 years.
measure: The modified Medical Research Council (mMRC) dyspnea scale
timeFrame: From enrollment to end of observation att 3 years.
measure: The Dyspnea-12 questionnaire
timeFrame: From enrollment to end of observation att 3 years.
measure: The EQ-5D questionnaire
timeFrame: From enrollment to end of observation att 3 years.
measure: Spirometry
timeFrame: From enrollment to end of observation att 3 years.
measure: One-minute sit-to-stand test (1-MSTST)
timeFrame: From enrollment to end of observation att 3 years.
measure: The Maximal Inspiratory Pressure (MIP) test
timeFrame: From enrollment to end of observation att 3 years.
measure: Blood gas analysis
timeFrame: From enrollment to end of observation att 3 years.
measure: Blood gas analysis
timeFrame: From enrollment to end of observation att 3 years.
measure: Blood gas analysis
timeFrame: From enrollment to end of observation att 3 years.
measure: Pulse oximetry
timeFrame: From enrollment to end of observation att 3 years.
measure: Chest X-ray
timeFrame: From enrollment to end of observation att 3 years.
measure: Computerised tomography (CT) of Thorax
timeFrame: From enrollment to end of observation att 3 years.
measure: Adverse events
timeFrame: 30 days post-operatively
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Department of Medical Sciences, Lung-, Allergy-, and Sleep Research, Uppsala University/Uppsala University Hospital
Study officials:
affiliation: Uppsala University Hospital
name: Andreas Palm, Md, PhD
role: PRINCIPAL_INVESTIGATOR
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