Clinical Trial: Long-term Effects of Thalidomide for Recurrent Gastrointestinal Bleeding Due to Vascular Malformation

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Long-term Effects of Thalidomide for Recurrent Gastrointestinal Bleeding Due to Vascular Malformation : An Open-label, Randomized, Parallel Controlled Study

Brief Summary:

Background: Repeated episodes of bleeding from gastrointestinal vascular malformations refractory to endoscopic or surgical therapy often pose a major therapeutic challenge.

Methods: The investigators performed a randomized, parallel controlled study of thalidomide as a therapy for recurrent gastrointestinal bleeding due to vascular malformation. Patients with at least six episodes of bleeding in the prior year due to vascular malformation were randomly grouped, prescribed a four-month regimen of either 25 mg of thalidomide or 100 mg of iron orally four times daily, and monitored for at least one year. The primary end point was defined as the patients whose rebleeds decreased from baseline by ≥ 50% at 12 months and the cessation of bleeding. Rebleeding was defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment. Secondary outcomes included the participants dependent on blood transfusions and changes from baseline in transfused packed red cell units, bleeding episodes, bleeding durations, and hemoglobin levels at 12 months. Statistical significance was defined at P < 0.05.

Detailed Summary:

Protocol Description:

This is an exploratory, randomized, parallel controlled study of thalidomide for recurrent gastrointestinal bleeding from vascular malformations. Informed consent was taken from all subjects and the Institute Ethics Committee approved the study protocol. All procedures were in accordance with the Declaration of Helsinki. The study was supported by no pharmaceutical funding.

Study design and Intervention:

From Nov. 2004 to Nov. 2007, patients with repeated episodes of chronic gastro-intestinal bleeding due to vascular malformations identified by oesophagogastroduodenoscopy, capsule endoscope or double-balloon endoscope were enrolled (according our enrollment criteria).

The patients were randomly assigned to receive a four-month course of either 25 mg of thalidomide or 100mg iron orally at daily time 6 a.m.,12 noon,6 p.m. and 10 p.m., respectively.

Randomization was performed through the proc plan procedure of Statistical Analysis Software (SAS), using the method of randomly permuted blocks of 4. Within each block, the number of patients allocated to each of the two treatments was equal. Each patient who met the inclusion criteria was consecutively assigned a random number in chronological order, which allocated him or her to one of the treatment groups. A blinded research nurse supervised patient randomization and drug administration.

In the case of an adverse event, the study medication was temporarily or permanently discontinued based on subject inclination and toxicity intolerance. Concomitant therapies, such as blood transfusions and other symptomatic treatments like iron supplementation, were performe
Sponsor: Shanghai Jiao Tong University School of Medicine

Current Primary Outcome:

• Participants Whose Rebleeds Decreased From Baseline by ≥ 50% at 12 Months [ Time Frame: baseline and 12 months ]
  The primary end point was defined as the patients whose rebleeds decreased from baseline by ≥ 50% at 12 months. Reduction of rebleeds = [(total bleeding episode at 12 months - total bleeding episodes at a year before randomization)/total bleeding episodes at a year before randomization(baseline)]*100%. Rebleeding was defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment.
• Cessation of Bleeding [ Time Frame: 52 months ]
  The cessation of bleeding was defined as repeated negative faecal occult blood test (FOBT) (monoclonal colloidal gold color technology) during our observation period. Rebleeding was defined based on a positive FOBT at any visit after treatment.

Original Primary Outcome: The primary end point was "cessation of bleeding" (defined as repeated negative faecal occult blood test after treatment), or "effective treatment" (defined as ≥50% reduction of numbers of bleeding episodes after treatment). [ Time Frame: one year ]

Current Secondary Outcome:

• Change From Baseline in Hemoglobin (Hb) Level at 12 Months [ Time Frame: baseline and 12 months ]
  The change from baseline in average hemoglobin (Hb) level(tested every month) at 12 months.
• Change From Baseline in Bleeding Episodes at 12 Months [ Time Frame: baseline and 12 months ]
  The Change from baseline in bleeding episodes at 12 months
• Change From Baseline in Bleeding Duration at 12 Months [ Time Frame: baseline and 12 months ]
  The change from baseline in bleeding duration at 12 months
• Participants Dependent on Blood Transfusions [ Time Frame: 52 months ]
  Numbers of participants dependent on blood transfusions
• Change From Baseline in Total Transfused Red Cell Requirements at 12 Months [ Time Frame: baseline and 12 months ]
  Change of total transfused red cell requirements at 12 months after randomization from one year before baseline in transfusion dependent patients

Original Secondary Outcome: The secondary end points were reductions in blood transfusion requirements and in the duration of bleeding, rise of Hb values. [ Time Frame: one year ]

Information By: Shanghai Jiao Tong University School of Medicine

Dates:
Date Received: August 24, 2009
Date Started: November 2004
Date Completion:
Last Updated: November 17, 2015
Last Verified: August 2009