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

Rib Fractures Clinical Trial

— PAROS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04745520
• Other study ID #: 2019-01688
• Status: Recruiting
• Phase: N/A
• Start date: March 12, 2021
• Est. completion date: March 2024

Study information

• Verified date: May 2022
• Source: University Hospital, Geneva
• Contact: Benoît Bédat, MD
• Phone: +41795904475
• Email: benoit.bedat[@]hcuge.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: March 2024
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fractures, Bone
• Rib Fractures

Intervention

Device:
• Rib fixation
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

Drug:
• Analgesia
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.

Locations

Country	Name	City	State
Switzerland	Unit of Thoracic and Endocrine Surgery, University Hospitals of Geneva	Geneva

Sponsors (3)

Lead Sponsor	Collaborator
Benoît Bédat	Centre Hospitalier Universitaire Vaudois, Hôpital du Valais

Country where clinical trial is conducted

Switzerland, 

References & Publications (9)

de Moya M, Bramos T, Agarwal S, Fikry K, Janjua S, King DR, Alam HB, Velmahos GC, Burke P, Tobler W. Pain as an indication for rib fixation: a bi-institutional pilot study. J Trauma. 2011 Dec;71(6):1750-4. doi: 10.1097/TA.0b013e31823c85e9. — View Citation

Fabricant L, Ham B, Mullins R, Mayberry J. Prolonged pain and disability are common after rib fractures. Am J Surg. 2013 May;205(5):511-5; discusssion 515-6. doi: 10.1016/j.amjsurg.2012.12.007. — View Citation

Fitzgerald MT, Ashley DW, Abukhdeir H, Christie DB 3rd. Rib fracture fixation in the 65 years and older population: A paradigm shift in management strategy at a Level I trauma center. J Trauma Acute Care Surg. 2017 Mar;82(3):524-527. doi: 10.1097/TA.0000000000001330. — View Citation

Gordy S, Fabricant L, Ham B, Mullins R, Mayberry J. The contribution of rib fractures to chronic pain and disability. Am J Surg. 2014 May;207(5):659-62; discussion 662-3. doi: 10.1016/j.amjsurg.2013.12.012. Epub 2014 Jan 31. — View Citation

Katz J, Jackson M, Kavanagh BP, Sandler AN. Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin J Pain. 1996 Mar;12(1):50-5. — View Citation

Kerr-Valentic MA, Arthur M, Mullins RJ, Pearson TE, Mayberry JC. Rib fracture pain and disability: can we do better? J Trauma. 2003 Jun;54(6):1058-63; discussion 1063-4. — View Citation

Marasco S, Lee G, Summerhayes R, Fitzgerald M, Bailey M. Quality of life after major trauma with multiple rib fractures. Injury. 2015 Jan;46(1):61-5. doi: 10.1016/j.injury.2014.06.014. Epub 2014 Jun 21. — View Citation

Peek J, Smeeing DPJ, Hietbrink F, Houwert RM, Marsman M, de Jong MB. Comparison of analgesic interventions for traumatic rib fractures: a systematic review and meta-analysis. Eur J Trauma Emerg Surg. 2019 Aug;45(4):597-622. doi: 10.1007/s00068-018-0918-7. Epub 2018 Feb 6. — View Citation

Wu WM, Yang Y, Gao ZL, Zhao TC, He WW. Which is better to multiple rib fractures, surgical treatment or conservative treatment? Int J Clin Exp Med. 2015 May 15;8(5):7930-6. eCollection 2015. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Anxiety and Depression.	hospital anxiety and depression scale (HADS). Score 0-21. 21 = severe depression or anxiety	At recruitment (baseline)
Secondary	Anxiety and Depression.	hospital anxiety and depression scale (HADS). Score 0-21. 21 = severe depression or anxiety	One month after injury
Secondary	Anxiety and Depression.	hospital anxiety and depression scale (HADS). Score 0-21. 21 = severe depression or anxiety	Two months after injury
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	Analgesic medication at home	After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire.	One month after injury
Secondary	Analgesic medication at home	After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire.	Two months after injury
Secondary	Analgesic medication at home	After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire.	Three months after injury
Secondary	Analgesic medication at home	After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire.	Six months after injury
Secondary	Analgesic medication at home	After discharge, analgesic medication (type and amount) is tracked using a custom questionnaire.	Twelve months after injury
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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