Statins and Selective Cyclooxygenase-2 Receptor Inhibitors in Blunt Chest Trauma

NCT01623921 | Unknown

• 1 other identifier: TASMC-08-WAA-026911-TLV
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Lung contusion affects 17%-25% of adult blunt trauma patients, and is the leading cause of death from blunt thoracic injury. Statins are lipid-lowering drugs with recently suggested anti-inflammatory and antioxidant properties. Cyclo-oxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins (PG), and evidence suggests that COX-2 plays an important role in the pathogenesis of acute lung injury (ALI). Aims: The current study aims at evaluating the beneficial effects of statins and COX-2 receptor inhibitors on ALI elicited by blunt trauma to the chest. Methods: After approval by the institutional ethics and a scientific committee, and obtaining informed consent , patients admitted to the emergency department (ED) due to blunt trauma with a diagnosis of lung contusion will be enrolled in the study.The effects of statins and COX 2 inhibitors on ALI will be assessed by recording clinical parameters and measuring inflammatory mediators levels in the serum and in the bronchoalveolar space. Expected results: The investigators expect to find that the proposed treatment will be effective in reducing ALI burden. The investigators also suppose that using a combination of those drugs will synergistically potentiate their effect on ALI.

Conditions

Blunt Chest Trauma; Acute Respiratory Distress Syndrome

Keywords

Lung; Contusion; Injury; Cyclooxygenase; Statin

Outcome Measures

Primary Outcomes (1)

• 1. Signs of ALI, i.e., pneumonia, adult respiratory distress syndrome [ARDS]

  1\. Signs of ALI, i.e., pneumonia, adult respiratory distress syndrome \[ARDS\] according to following criteria: 1. Suspected or proven infection 2. Hypoxemia: PaO2/FiO2is ≤300 mm HgBilateral infiltrates consistent with pulmonary edema 3. Positive-pressure mechanical ventilation through an endotracheal tube 4. No clinical evidence of left atrial hypertension to explain bilateral infiltrates 5. Presence of at least three of the four SIRS criteria. If only two criteria are evidenced, one must be temperature or WBC

  3 days

Study Arms (4)

control

OTHER

Group 1: control :(standard care treatment for individual lung contusion inluding analgesia with paracetamol/dypiron/ tramal)

Drug: standard care treatment

Celecoxib

ACTIVE COMPARATOR

Group 2: Celecoxib 200 mg × 2/d+:(standard care treatment for individual lung contusion inluding analgesia with paracetamol/dypiron/ tramal)

Drug: Celecoxib

rosuvastatin

ACTIVE COMPARATOR

Group 3: Rosuvastatin 40mg × 1/d+:(standard care treatment for individual lung contusion inluding analgesia with paracetamol/dypiron/ tramal)

Drug: Rosuvastatin

Combined therapy

ACTIVE COMPARATOR

Group 4: Combined therapy with Celecoxib 200 mg× 2/d + Rosuvastatin 40× 1/d +:(standard care treatment for individual lung contusion inluding analgesia with paracetamol/dypiron/ tramal)

Drug: Combined therapy

Interventions

standard care treatment DRUG

Group 1: control :(standard care treatment for individual lung contusion inluding analgesia with paracetamol/dypiron/ tramal)

control

Celecoxib DRUG

Celecoxib 200 mg × 2/d+:(standard care treatment for individual lung contusion inluding analgesia with paracetamol/dypiron/ tramal)

Celecoxib

Rosuvastatin DRUG

Rosuvastatin 40mg × 1/d+:(standard care treatment for individual lung contusion inluding analgesia with paracetamol/dypiron/ tramal)

rosuvastatin

Combined therapy DRUG

Combined therapy with Celecoxib 200 mg× 2/d + Rosuvastatin 40× 1/d +:(standard care treatment for individual lung contusion inluding analgesia with paracetamol/dypiron/ tramal)

Combined therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 18 years of age
• Diagnosis of lung contusion by physical examination, chest xrays, history by the patient, accompanying persons or police.
• Ability to understand and accept the trial procedures and to sign an informed consent form in accordance with national legislation.
• Admission to ward

You may not qualify if:

• Penetrating trauma
• Current use of lipid-lowering therapy, use of non steroidal anti-inflammatory drugs.
• Current use of postmenopausal hormone-replacement therapy
• Evidence of hepatic dysfunction (an alanine aminotransferase level more than twice the upper limit of the normal range), a creatine kinase level more than three times the upper limit of the normal range.
• Creatinine level higher than 2.0 mg/dl
• Known uncontrolled hypertension (systolic blood pressure \>190 mm Hg or diastolic blood pressure \>100 mm Hg
• History of uncontrolled hypothyroidism (thyroid-stimulating hormone level\> 1.5 times the upper limit of the normal range)
• Psychiatric disorders
• Pregnancy
• Known allergy or intolerance to one of the protocol drug

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead

Study Sites (1)

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome; Contusions; Wounds and Injuries

Interventions

Celecoxib; Rosuvastatin Calcium; Psychotherapy, Multiple

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Wounds, Nonpenetrating

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Pyrimidines; Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Avi A Weinbroum, MD

CONTACT

3-6973237; draviw@tasmc.health.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Division of Research & Development

Study Record Dates

• First Submitted: June 17, 2012
• First Posted: June 20, 2012
• Study Start: August 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: June 20, 2012

Record last verified: 2012-06

Locations

IL (1)