Clinical trial NCT01203046: Early Short-term Antibiotic Therapy in Penetrating Abdominal Trauma, 3 vs 7 Days
Official title: SP1 - Early Short-term Antibiotic Therapy in Penetrating Abdominal Trauma, 3 vs 7 Days
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SURGICAL SITE INFECTION
Keywords: DURATION OF THERAPY
PENETRATING ABDOMINAL TRAUMA
Lead sponsor: Pinango, Silvia M. L., M.D.
Sponsor class: INDIV
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2010-09-16
Enrollment: 56
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Abdominal penetrating trauma represents a frequent cause of consult into emergency rooms in Venezuela. Accidents and violence at Hospital "Miguel Perez Carreño" along april 2009 were represented by gunshots and stabbing wounds which 8th. and 18th cause for medical attention respectively within a total of 76 cases. Likewise gunshot wounds reach the first cause of morbility into general surgery services with 21 cases and the stabbing wounds the 12th cause with 12 cases within the same period.

Early therapy is defined as the antibiotic dose administrated within the first 12 hours after the trauma. Abdominal cavity contamination by micro-organism is not synonymous of stablished infection, the extension of contamination and intensity of reaction should be enough in order to allow the inflammatory focus developing.

Abdominal cavity needs at least 12 - 24 hours of exposure to the infectious material to allow the stablishment of such infection. Origin and amount of contaminant material influence the size of inoculated bacteria and the speed that infection develops.

There is not an absolute criteria to determine when intrabdominal contamination progress to an established infection. Surgeons decides the must adequated therapy according to clinical history, radiology tests and findings during surgery.

Selected patients for early antibiotic therapy in penetrating abdominal trauma includes those with traumatic intestinal wounds with less than 12 hours of evolution and those with gastroduodenal wounds lesser than 24 hours as well.

There are different antibiotics indicated for intrabdominal infections. Ertapenem is a low resistance carbapenem with a broad spectrum into microbial flora presenting in penetrating abdominal trauma. Its media life and blood therapeutic levels allows the use of an unique dose within the first 24 hours of trauma.

This research protocol has been designed according to established patterns for clinical investigation and our goal is to achieve criteria in decision making about antibiotic administration in patients with penetrating abdominal trauma and evaluate the security of an Early short term antibiotic therapy with Ertapenem 3 days vs 7 days, decreasing hospital costs related to indiscriminate use of antibiotics.

Detailed description: General objectives The object of this research is to evaluated the impact of Early short-term antibiotic therapy with Ertapenem, 3 vs 7 days, upon clinical postoperatory evolution in patients with penetrating abdominal trauma at emergency room of "Miguel Perez Carreño" Hospital

Specific objectives

1. To determine the incidence of postoperatory infectious complications in patients with penetrating abdominal trauma under Early short term antibiotic therapy with Ertapenem.
2. To establish the efficacy of Early short term antibiotic therapy 3 days with Ertapenem versus systematic administration of the same antibiotic up to the 7th day after surgery in order to prevent postoperatory infections.
3. To identify the risk factors that predispose the appearance of infectious complications in patients with penetrating abdominal trauma.

Investigation type This will be a prospective, comparative, double blind, randomized, experimental clinical trial in patients with penetrating abdominal trauma, who attend the emergency room of Dr. "Miguel Perez Carreño" Hospital between February and July 2010.

Therapy. Surgery will be perform within a period no longer than twelve hours since time of trauma. Culture samples from abdominal cavity will be taken during the surgery in order to identify the bacterial prevalence and its sensibility to antibiotics.

Ertapenem will be administrated within the first 2 hours of Hospital´s admission and the next two days after surgery. At day four, patients will be assigned to different groups A or B, according to they entrance number into this trial.

Group A treatment will be continued with Ertapenem until 7th day. Group B antibiotic therapy will be stopped.

Patients follow up will be done during the first 10 days after trauma in two phases:

1. First 7 days patients will be controlled by a daily evaluation and the data will be recorded according to variables in the control sheet (Appendix 3).
2. Patients with evolution as follows, will be treated under medical criteria and cultures results:

   1. Temperature 38,5 °C or higher more than 24 hours within the first 7 postoperatory days.
   2. Sustained WBC count higher than 14,000 or increase after 48 hrs. Postoperatory.
   3. Postoperatory complications such as gastric or intestinal fistula, purulent drainage, intrabdominal abscess.
3. On day 10 a new evaluation of patients will be performed and recorded in the control sheet (Appendix 4).

Evaluation variables. Information will be recorded by full register of standard control sheets which includes: admittance date, medical history number, age, sex, clinical conditions, associated comorbidity, surgical findings, time since trauma, surgery time, and starting time of antibiotic administration (Appendix 1).

Penetrating abdominal trauma scale will be applied in order to determine the seriousness of trauma and its potential general echoes (Appendix 2).

During the postoperatory period the control sheet will include: WBC count, albumin, lymphocyte, local conditions of the surgical wound and penetration site wound at the abdominal wall, complications(Appendix 3).

After patient discharge, they will be appointed and evaluated 10 to 12 days after surgery and the following items will be recorded: local conditions of the surgical wound, and penetration site wound, complications. (Appendix 4).

Data from excluded patients will be recorded by exclusion causes and their evolution (Appendix 5). Result of sample cultures taken during surgery and its antibiogram will be reported (Appendix 6).

Operations plan timetable

1. Problem identification request and project design. October 2009 - Feb 2010.
2. Authorization request to the Bioethics Board of "Dr. Miguel Perez Carreño" Hospital. Feb 2010.
3. Authorization request to the Technical Commission of "Dr. Miguel Perez Carreño" Hospital. Feb 2010
4. Development and execution. Feb Nov - 2010.
5. Data analysis. November 2010.
6. Presentation and introduction for publication.

Data processing analysis.

To establish non-inferiority of the use of the therapy with ertapenem between three days versus 7 days of treatment, was considered a significance level of 5%, 95% confidence interval, a power of 80% and in the group control of 60%, a margin of not less 10% is considered of no clinical importance. For a balanced design of type n1 = n2 r = 1. Still needed 26 patients per group. The period of advance recruitment of patients was 6 months.

Ethical aspects. It will be required and informed consent to individuals whom enter to this study, after explaining to them what is all about, the benefits and the possible risks, they wil be asked for their signatures or the signatures of closest relatives at the entrance time. (Appendix 6).

Eligibility criteria: Inclusion Criteria:

1. Patients with penetrating abdominal trauma who attended the emergency room within 12 hours after trauma, admitted to an exploratory laparotomy.
2. Patients aged 12 to 65 years.

Exclusion Criteria:

1. Clinical history of immunologic diseases, cancer, use of immunosuppressors, steroids, malnutrition, morbid obesity.
2. Concomitant pathology at admittance: urinary infections, respiratory infections, hepatitis, viral diseases.
3. Associated open bone fractures.
4. Patients with hemodynamic instability during pre or peroperative.

Primary outcomes:
measure: Surgical Site Infection
timeFrame: 10 days
measure: Other Complications
timeFrame: 10 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: IVSS Dr. MIGUEL PEREZ CARREÑO HOSPITAL
name: SILVIA M. PIÑANGO, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IVSS Dr. MIGUEL PEREZ CARREÑO HOSPITAL
name: LUIS R. LEVEL, MD FACS
role: STUDY_CHAIR
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