Randomized Clinical Trial of Rib Fixation Versus Medical Analgesia in Uncomplicated Rib Fractures on Pain Control.

Study Overview
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Brief Summary
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Uncomplicated costal fractures often result in persistent pain over the long term. Indeed, cohort studies showed that at 6 months, 22% of patients still had pain and 56% had functional disability. The impact of costal fractures on quality of life is underestimated. The socio-psycho-economic consequences are substantial. Previous studies have shown that an important factor for persistent pain and functional disability is the intensity of the initial pain. However, preliminary studies have shown promising results with surgical fixation of rib fractures: reduced need for analgesic drugs, reduced pain at 1 month, reduced complications and improved motor skills in patients over 65 years of age. To date, the only clinical trials that exist focused on the fixation of complicated rib dislocations. While fixation of uncomplicated rib fractures is a common practice, no randomized studies have been conducted to evaluate its impact on pain and quality of life in the medium and long term. In this context, the aim of our randomized study is to compare pain at 2 months between operated and non-operated patients with uncomplicated rib fractures.

Detailed Description
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Background. Until recently, functional disability and chronic pain and following uncomplicated rib fractures have been scarcely studied. Studies described persistent pain and disability in, respectively, 59% and 76% of patients at two months, and in 22% and 53% of patients at 6 months. In a retrospective study including 216 patients with an isolated thoracic injury, only 34.2% of patients had a good recovery at one year and the six-month return to work rate is of 63%. Persistent pain and disability following rib fractures therefore result in a large psycho-socio-economic impact for health-care system. The only predictive factor for persistent pain and disability is the pain intensity within the first few days after injury. Similarly, the intensity of pain within the first days after thoracotomy predicts long-term post-thoracotomy pain. In a recent meta-analysis, epidural analgesia provides better acute pain relief than intravenous, paravertebral, and intercostal interventions. While meta-analyses conclude that operative fixation of complicated flail chest provide better outcome, the impact of surgery on pain in uncomplicated rib fracture is seldom studied. Some retrospective studies showed promising results of rib fixation with surgery in patients with uncomplicated rib fractures: A study showed that rib fixation reduced postoperative analgesic requirements. Similarly, another study showed that pain was significantly reduced one month after surgery as compared to a non-surgical approach. Finally, it has been recently observed a decreased mortality and respiratory complications after surgery in patients over 65 years old as well as a better functional status at two weeks, two months, and four months. Trial objectives. No previous studies have provided definitive evidence for recommending rib fixation over simple pain medication to control pain. Our hypothesis is that a surgical approach may have further benefits as compared to a conservative treatment. The primary objective of the study is to compare pain two months after injury between two groups: group 1) patients who are treated with surgery and analgesic treatment; and group 2) patients who are treated with analgesic treatment alone. The secondary objective is to perform a longitudinal analysis over one year of the following parameters: amount of pain medication, quality of life, anxiety and depression, pulmonary capacity, return to work, and adverse events. Financial aspects are also investigated.

Official Title
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Comparison of Rib Fixation With Medical Analgesia in Patients With Uncomplicated Rib Fractures on Pain Control: a Multi-center Randomized Clinical Trial

Conditions
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Rib Fractures

Intervention / Treatment
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* Device: Rib fixation
* Drug: Analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 2 rib fractures At least 1 dislocated rib fracture Fractures accessible to surgery Thoracic trauma no more than two days prior to screening for inclusion Thoracic epidural analgesia Written informed consent Exclusion Criteria: Any other concomitant fractures excepted clavicle fracture Respiratory distress syndrome according to the Berlin definition Presence of >1.5 liter of blood drained from the pleural space Hemostasis disorder defined by any of the following criteria: Platelet count < 70'000/mm3, International Normalized Ratio (INR) > 1.2 (Prothrombin < 70%) activated partial thromboplastin time (aPTT) ≥ 60 seconds drugs such as: P2Y12 antagonists (clopidogrel, prasugrel) and glycoprotein IIb/IIIa antagonists (abciximab, tirofiban) Pathological rib fracture due to metastasis Hemodynamic instability: systolic blood pressure < 100 mmHg and heart rate > 100 beats per minute Neurologic disorder: Glasgow Coma Score < 13 in the initial 24 hours, or intracerebral, epidural, subdural, or subarachnoid hemorrhages, or cerebral contusion Titanium allergy Known or suspected non-compliance to medical therapy due to drug or alcohol abuse Age <18 years old Women who know they are pregnant or breast feeding Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This pragmatic trial is a multi-center, two-arm, parallel-group, superiority randomized-controlled trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rib fixation (medical devices)<br>Surgery and pain medication. The pain of patients will be treated with rib fixation and pain medication. | Device: Rib fixation<br>* Rib fixation is performed by a senior surgeon. The patient is under general anesthesia. A thoracotomy focused on the fracture is performed to optimize access to the rib to be repaired. Video-assisted thoracic surgery (VATS) can be performed to better localize rib fractures. Significant muscle division is avoided. Removal of the periosteum is not required. The broken rib segments are approximated with forceps and the medical devices are used to fix the fracture. The medical devices are implemented according to the manufacturers' recommendations. The goal is to stabilize the chest wall. It is not useful to fix all fractures to stabilize the wall. A chest tube can be placed at the end of the operation. Medical devices The following medical devices can be used: MatrixRIB™, De Puy Synthes Companies, Zuchwill, Switzerland STRATOS™, MedXpert GmbH, Heitersheim, Germany NiTi Fixing PlatesTM, IAWAI, Yandzhou, China<br>Drug: Analgesia<br>* Epidural analgesia is continuing for 24 to 72 hours post-randomization to maximize outcome benefits. Afterwards, paracetamol, NSAID and/or opioid treatment are used according to pain severity. In case of opioid use, morphine treatment is preferred. However, other opioid drugs or doses can be considered to better customize the treatment.<br>|
| Active Comparator: Pain medication (comparator treatment)<br>Pain medication only. | Drug: Analgesia<br>* Epidural analgesia is continuing for 24 to 72 hours post-randomization to maximize outcome benefits. Afterwards, paracetamol, NSAID and/or opioid treatment are used according to pain severity. In case of opioid use, morphine treatment is preferred. However, other opioid drugs or doses can be considered to better customize the treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain severity | Pain level reported by the participant, as assessed via the first part of the French version of the brief pain inventory (BPI) questionnaire. 0-10 scale. 10 indicating worst pain | Two months after injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain severity | Pain level reported by the participant, as assessed via the first part of the French version of the brief pain inventory (BPI) questionnaire. 0-10 scale. 10 indicating worst pain | At recruitment (baseline) | 
| Pain severity | Pain level reported by the participant, as assessed via the first part of the French version of the brief pain inventory (BPI) questionnaire. 0-10 scale. 10 indicating worst pain | One month after injury | 
| Pain severity | Pain level reported by the participant, as assessed via the first part of the French version of the brief pain inventory (BPI) questionnaire. 0-10 scale. 10 indicating worst pain | Three months after injury | 
| Pain severity | Pain level reported by the participant, as assessed via the first part of the French version of the brief pain inventory (BPI) questionnaire. 0-10 scale. 10 indicating worst pain | Six months after injury | 
| Pain severity | Pain level reported by the participant, as assessed via the first part of the French version of the brief pain inventory (BPI) questionnaire. 0-10 scale. 10 indicating worst pain | Twelve months after injury | 
| Anxiety and Depression. | hospital anxiety and depression scale (HADS). Score 0-21. 21 = severe depression or anxiety | At recruitment (baseline) | 
| Anxiety and Depression. | hospital anxiety and depression scale (HADS). Score 0-21. 21 = severe depression or anxiety | One month after injury | 
| Anxiety and Depression. | hospital anxiety and depression scale (HADS). Score 0-21. 21 = severe depression or anxiety | Two months after injury | 
| Neuropathic pain | The French questionnaire Douleur Neuropathique en 4 Questions (DN4) is completed by an investigator during follow-up visits. The DN4 questionnaire was developed to diagnose polyneuropathy. Three items are linked with neuropathic pain examination, and seven items to pain symptoms. Score 0-10. Score >4 indicates neuropathic pain. | Two months after injury | 
| Neuropathic pain | The French questionnaire Douleur Neuropathique en 4 Questions (DN4) is completed by an investigator during follow-up visits. The DN4 questionnaire was developed to diagnose polyneuropathy. Three items are linked with neuropathic pain examination, and seven items to pain symptoms. Score 0-10. Score >4 indicates neuropathic pain. | Six months after injury | 
| Pain interference | The last items of the BPI questionnaires measure how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others and sleep. BPI pain interference is scored as the mean of the seven items. Score 0-10. 10 = high interference of pain with activities. | At recruitment (baseline) | 
| Pain interference | The last items of the BPI questionnaires measure how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others and sleep. BPI pain interference is scored as the mean of the seven items. Score 0-10. 10 = high interference of pain with activities. | One month after injury | 
| Pain interference | The last items of the BPI questionnaires measure how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others and sleep. BPI pain interference is scored as the mean of the seven items. Score 0-10. 10 = high interference of pain with activities. | Two months after injury | 
| Pain interference | The last items of the BPI questionnaires measure how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others and sleep. BPI pain interference is scored as the mean of the seven items. Score 0-10. 10 = high interference of pain with activities. | Three months after injury | 
| Pain interference | The last items of the BPI questionnaires measure how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others and sleep. BPI pain interference is scored as the mean of the seven items. Score 0-10. 10 = high interference of pain with activities. | Six months after injury | 
| Pain interference | The last items of the BPI questionnaires measure how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others and sleep. BPI pain interference is scored as the mean of the seven items. Score 0-10. 10 = high interference of pain with activities. | Twelve months after injury | 
| Health and well being | The 36-Item Health Survey (SF-36) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Score: 0-100. 100 = better functioning | At recruitment (baseline) | 
| Health and well being | The 36-Item Health Survey (SF-36) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Score: 0-100. 100 = better functioning | Two months after injury | 
| Health and well being | The 36-Item Health Survey (SF-36) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Score: 0-100. 100 = better functioning | Six months after injury | 
| Analgesic medication during hospitalisation | During hospitalization, each day since the enrolment, amount and type of analgesic medication are recorded from the computerized patient record system. | At recruitement (baseline) | 
| Analgesic medication at home | After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire. | One month after injury | 
| Analgesic medication at home | After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire. | Two months after injury | 
| Analgesic medication at home | After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire. | Three months after injury | 
| Analgesic medication at home | After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire. | Six months after injury | 
| Analgesic medication at home | After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire. | Twelve months after injury | 
| Productivity & return to work | The work productivity and activity impairment (WPAI) questionnaire is used. It assesses impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Score 0-10. 10 = high impairment | One month after injury | 
| Productivity & return to work | The work productivity and activity impairment (WPAI) questionnaire is used. It assesses impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Score 0-10. 10 = high impairment | Two months after injury | 
| Productivity & return to work | The work productivity and activity impairment (WPAI) questionnaire is used. It assesses impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Score 0-10. 10 = high impairment | Three months after injury | 
| Productivity & return to work | The work productivity and activity impairment (WPAI) questionnaire is used. It assesses impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Score 0-10. 10 = high impairment | Six months after injury | 
| Productivity & return to work | The work productivity and activity impairment (WPAI) questionnaire is used. It assesses impairments in both paid work and unpaid work. It measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. Score 0-10. 10 = high impairment | Twelve months after injury | 
| Pulmonary function | Forced vital capacity (FVC, % predicted) measured according to the recommendations of the European Respiratory Society. The best value of at least three tests is recorded. | Two months after injury | 
| Pulmonary function, forced vital capacity | Forced vital capacity (FVC, % predicted) measured according to the recommendations of the European Respiratory Society. The best value of at least three tests is recorded. | Six months after injury | 
| Pulmonary function, peak expiratory flow | Peak expiratory flow (PEF, L/min) measured according to the recommendations of the European Respiratory Society. The best value of at least three tests is recorded. | Two months after injury | 
| Pulmonary function, peak expiratory flow | Peak expiratory flow (PEF, L/min) measured according to the recommendations of the European Respiratory Society. The best value of at least three tests is recorded. | Six months after injury | 
| Pulmonary function, sniff nasal inspiratory pressure | sniff nasal inspiratory pressure (in in cmH2O) measured according to the recommendations of the European Respiratory Society. The best value of at least three tests is recorded. | Two months after injury | 
| Pulmonary function, sniff nasal inspiratory pressure | sniff nasal inspiratory pressure (in in cmH2O) measured according to the recommendations of the European Respiratory Society. The best value of at least three tests is recorded. | Six months after injury | 
| Pulmonary function, inspiratory pressure | Maximum inspiratory pressure (in in cmH2O) measured according to the recommendations of the European Respiratory Society. The best value of at least three tests is recorded. | Two months after injury | 
| Pulmonary function, inspiratory pressure | Maximum inspiratory pressure (in in cmH2O) measured according to the recommendations of the European Respiratory Society. The best value of at least three tests is recorded. | Six months after injury | 
| Length of hospital stay | Length of hospital stay is reported in days from the day of hospitalization until the hospital discharge. The length of convalescence stay is also reported. | from admission to discharge, up to four weeks | 
| Total costs | Costs are reported at the end of the follow-up period (12 months) in swiss francs. They include costs for hospital treatment and costs for medication. | Twelve months after injury | 
| Adverse events | We collect safety outcomes in accordance with international standards (ISO 14155 and ICH-GCP) | From inclusion to the end of the study, up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thoracic trauma, rib fixation, medical device