Autologous Fibrin Glues for Fistulas Closure

NCT ID: NCT01561066

Last Updated: 2013-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2012-01-31

Brief Summary

Adjuvant use of fibrin glue in the fistula tract may promote healing in low-output enterocutaneous fistulas. However, there are only few studies that report autologous glue application in a larger patient group or clinical-controlled studies in this setting. The aim of this study was to investigate the efficacy and safety of autologous platelet-rich fibrin glue (PRFG) in the treatment of low-output digestive fistulas and compare them with conservative management without the use of adjuvant application of FG into the fistulous tract.

Detailed Description

The sudden appearance of intestinal contents draining from an abdominal incision is an emotionally devastating experience for both patients and surgeons. An enterocutaneous fistulas (ECF) is an abnormal communication between the bowel lumen and skin, often associated with fluid and electrolyte abnormalities, malnutrition, and sepsis. It is reported that spontaneous fistula closure rates vary from 15% to 71% after conservative treatment with wound care, control of infection, and nutritional support. Sufficient time should be allotted for the ECF to heal with conservative treatment, which also results in long-term discomfort.

Adjuvant use of fibrin glue (FG) in the fistula tract may promote healing in low-output ECF. Containing high concentrations of human fibrinogen and thrombin, FG have been used extensively in many surgical fields as a biological adhesive system for tissue adhesion or hemostasis. Different types of FG are now employed: commercially produced and homemade autologous adhesives. Currently available FDA-approved commercial products such as Tisseel, Artiss (Baxter, Westlake Village, CA, USA), and Evicel (Johnson & Johnson, Somerville, NJ, USA) are widely used in clinical applications. Risks of infection transmission, allergic reactions, and also the high cost, however, still make autologous FG attractive. Additionally, in comparison with other adhesives, autologous compounds have several advantages in terms of biocompatibility and biodegradation.

The aim of this study was to investigate the efficacy and safety of autologous platelet-rich fibrin glue (PRFG) in the treatment of low-output digestive fistulas and compare them with conservative management without the use of adjuvant application of FG into the fistulous tract.

Conditions

Enterocutaneous Fistulas; Intra-abdominal Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

conservative therapy

Conservative therapy includes orrection of electrolytic disturbances, suppression of gastric/intestinal secretion with octreotide, nutritional support.

Group Type: SHAM_COMPARATOR

Octreotide

Intervention Type: DRUG

subcutaneous injection, 0.3mg/8h until enteral nutrition resolution

Application of autologous PRFG

The application of the glues through the external opening of the fistula was controlled by the drainage tube, which was based on fistulography to assure total occlusion of the internal hole. To allow the adhesion of the fibrin glues patch, all fistulous tracts were debrided to produce a smooth surface. At the time of procedures, the two components were mixed together to yield a gelatinous substance. After the FG was instilled, any redundant glue was removed from the external openings.

Group Type: ACTIVE_COMPARATOR

Autologous platelet-rich fibrin glue (PRFG)

Intervention Type: PROCEDURE

1. Preparation of autologous platelet-rich fibrin glues (PRFG) The platelet-rich plasma (PRP) was separated by centrifugation from 300-400 ml whole blood for 6 min at 1000g, 22°C twice, keeping most of the platelets (50%-60%) in the plasma fraction. For 50g PRP from each patient, with citric acid (2.84mM) lowering and NaHCO3 (75mM) adjusting the PH value, thrombin solution was produced. On the other hand, cryoprecipitate was produced from the rest of the plasma. Frozen at -80°C for at least 6h and then thawed at 4°C, PRP went through centrifugation at 4000rpm/min for 5min.

2. PRFG application The application of the glues through the external opening of the fistula was controlled by the drainage tube through a double-syringe system with distal mixing device. The distance was based on fistulography to assure total occlusion of the internal hole. After the FG was instilled, any redundant glue was removed from the external openings.

Octreotide

Intervention Type: DRUG

subcutaneous injection, 0.3mg/8h until enteral nutrition resolution

Interventions

Autologous platelet-rich fibrin glue (PRFG)

1. Preparation of autologous platelet-rich fibrin glues (PRFG) The platelet-rich plasma (PRP) was separated by centrifugation from 300-400 ml whole blood for 6 min at 1000g, 22°C twice, keeping most of the platelets (50%-60%) in the plasma fraction. For 50g PRP from each patient, with citric acid (2.84mM) lowering and NaHCO3 (75mM) adjusting the PH value, thrombin solution was produced. On the other hand, cryoprecipitate was produced from the rest of the plasma. Frozen at -80°C for at least 6h and then thawed at 4°C, PRP went through centrifugation at 4000rpm/min for 5min.

2. PRFG application The application of the glues through the external opening of the fistula was controlled by the drainage tube through a double-syringe system with distal mixing device. The distance was based on fistulography to assure total occlusion of the internal hole. After the FG was instilled, any redundant glue was removed from the external openings.

Intervention Type: PROCEDURE

Octreotide

subcutaneous injection, 0.3mg/8h until enteral nutrition resolution

Intervention Type: DRUG

Other Intervention Names

Octreotide Acetate Injection, Novartis, Switzerland

Eligibility Criteria

Inclusion Criteria

• older than 18 years
• presence of one or more fistulas
• fistulas of low-output volume (< 200ml/24h)

• mental handicap
• extreme thinness
• fistulous tract length < 2 cm
• fistulous tract diameter > 1 cm
• entero-atmospheric fistulas
• Crohn's disease-related fistulas
• any conditions that might impede spontaneous closure of the fistula, such as complex tracts, associated abscesses, residual disease, foreign bodies or distal obstruction
• any conditions that might increase the risk of auto-transfusion, including hypertension, or diabetes; and acquired immune deficiency syndrome (AIDS)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jinling Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Jianan Ren

Clinical professor, Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Surgery, Jinling Hospital

Nanjing, Jiangsu, China

Countries

China

References

Wu X, Ren J, Gu G, Wang G, Han G, Zhou B, Ren H, Yao M, Driver VR, Li J. Autologous platelet rich fibrin glue for sealing of low-output enterocutaneous fistulas: an observational cohort study. Surgery. 2014 Mar;155(3):434-41. doi: 10.1016/j.surg.2013.09.001. Epub 2013 Oct 29.

Reference Type: DERIVED

PMID: 24183344 (View on PubMed)

Other Identifiers

BRA2011232-1

Identifier Type: -

Identifier Source: org_study_id