Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: A randomized, double-blind trial

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Upper gastrointestinal bleeding (UGIB) is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB. A total of 245 cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days. Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0.03) and the 24-hour bleeding control end point (P = 0.01) in the subgroup of Child-Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of adverse events including thromboembolic events. Although no overall effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.

Related collections

Most cited references 22

Record: found
Abstract: found
Article: not found

Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators.

Gennaro D'Amico, Roberto de Franchis (2003)

Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis. The aim of this multicenter, prospective, cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis. A training set of 291 and a test set of 174 bleeding cirrhotic patients were included. Treatment was according to the preferences of each center and the follow-up period was 6 weeks. Predictive rules for 5-day failure (uncontrolled bleeding, rebleeding, or death) and 6-week mortality were developed by the logistic model in the training set and validated in the test set. Initial treatment controlled bleeding in 90% of patients, including vasoactive drugs in 27%, endoscopic therapy in 10%, combined (endoscopic and vasoactive) in 45%, balloon tamponade alone in 1%, and none in 17%. The 5-day failure rate was 13%, 6-week rebleeding was 17%, and mortality was 20%. Corresponding findings for variceal versus nonvariceal bleeding were 15% versus 7% (P =.034), 19% versus 10% (P =.019), and 20% versus 15% (P =.22). Active bleeding on endoscopy, hematocrit levels, aminotransferase levels, Child-Pugh class, and portal vein thrombosis were significant predictors of 5-day failure; alcohol-induced etiology, bilirubin, albumin, encephalopathy, and hepatocarcinoma were predictors of 6-week mortality. Prognostic reassessment including blood transfusions improved the predictive accuracy. All the developed prognostic models were superior to the Child-Pugh score. In conclusion, prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades. Initial treatment stops bleeding in 90% of patients. Accurate predictive rules are provided for early recognition of high-risk patients.

0 comments Cited 191 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study.

(1988)

We conducted a prospective study of 321 patients with cirrhosis of the liver and esophageal varices with no history of bleeding to see whether a comprehensive analysis of their clinical features and of the endoscopic appearances of their varices could help to identify those at highest risk for bleeding. Varices were classified endoscopically as suggested by the Japanese Research Society for Portal Hypertension. Patients were followed for 1 to 38 months (median, 23), during which 85 patients (26.5 percent) bled. Multiple regression analysis (Cox's model) revealed that the risk of bleeding was significantly related to the patient's modified Child class (an index of liver dysfunction based on serum albumin concentration, bilirubin level, prothrombin time, and the presence of ascites and encephalopathy), the size of the varices, and the presence of red wale markings (longitudinal dilated venules resembling whip marks) on the varices. A prognostic index based on these variables was devised that enabled us to identify a subset of patients with a one-year incidence of bleeding exceeding 65 percent. The index was prospectively validated on an independent sample of 75 patients with varices and no history of bleeding. We conclude that our prognostic index, which identifies groups of patients with one-year probabilities of bleeding ranging from 6 to 76 percent, can be used to identify candidates for prophylactic treatment.

0 comments Cited 149 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Improved patient survival after acute variceal bleeding: a multicenter, cohort study.

Edmund J. Bini, Padmaja Marathe, Qingxi Shen … (2003)

Existing literature indicates that the mortality rate with each variceal bleeding episode is 30-50%. Over the past 2 decades, there have been significant developments in the management of variceal bleeding. The effect of these developments on the natural history of variceal bleeding is unclear. Therefore, a retrospective, multicenter study was conducted to define the outcomes of variceal bleeding and to describe the patterns of current practice in the management of variceal bleeding. All patients with documented variceal bleeding hospitalized at four large county hospitals from January 1, 1997, to June 30, 2000, were included. Study outcomes were in-hospital, 6-wk, and overall mortality, rate of rebleeding, transfusion requirement, and length of stay. After discharge, patients were followed until death or study closure date, on June 30, 2000. A total of 231 subjects were included, and their in-hospital, 6-wk, and overall mortality rates were 14.2%, 17.5%, and 33.5%, respectively. The frequency of rebleeding during follow-up was 29%. Median length of total hospital stay was 8 days (0-34 days). Median number of packed red cell units transfused was 4 U (0-60 U). Upper endoscopy was performed in 95% of patients within 24 h, and endoscopic therapy was done in all but eight patients (ligation 64%, sclerotherapy 33%). Octreotide was administered in 74% of the patients. Portasystemic shunts were performed in 7.5% of the patients for controlling acute variceal bleeding. The mortality rate after variceal bleeding in this study was substantially lower than previously reported. This suggests that advances made in the management of variceal bleeding have improved outcomes after variceal bleeding.