Clinical Trial: Efficacy Study of Thalidomide in Gastrointestinal Vascular Malformation Related Bleeding

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A Randomised, Double-blind, Placebo-controlled Study of Thalidomide in Gastrointestinal Vascular Malformation Related Bleeding

Brief Summary:

Background: Repeated bleeding from gastrointestinal vascular malformations remains to be a major therapeutic challenge.

Methods: The investigators performed a randomised, double-blind, placebo-controlled, single centre study to assess the long-term efficacy and safety of thalidomide 100mg qn p.o. or placebo 100 mg qn p.o. administration for 4 months in subjects with recurrent gastrointestinal bleeding due to vascular malformations. 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 100mg of thalidomide or 100 mg of placebo orally one time 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. 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 changes from baseline in participants dependent on blood transfusions and 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:

Study design:

The study will be carried out as a single-centre, randomized, double-blind, parallel-group, placebo-controlled phase II study in subjects with recurrent gastrointestinal bleeding due to vascular malformations.

Subjects Enrollment and Assignment:

Approximately 100 patients aged between 40-85 years with recurrent gastrointestinal bleeding (melena and/or fresh hematemesis or positive FOBT) at least 6 times within one year, verified as vascular malformation by capsule endoscopies or enteroscopies at baseline.

Randomization was performed through the proc plan procedure of 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. Subjects who are eligible for randomisation will be given a subject number in consecutive order within blocks, and the investigational products packed corresponding to this number. The subject will be allocated to one of the two treatment groups, i.e. Thalidomide and placebo, according to a computer generated list provided by Pharmaceutical Co., Ltd. of Chang Zhou, China. If a subject discontinues from the study, the subject number will not be reused, and the subject will not be allowed to re-enter the study.

Intervention:

The included patients were prospectively randomized into two groups: the thalidomide group and the placebo group (Thalidomide group: Thalidomide p.o. 100 mg for 4 months, qn; Placebo group: Placebo for thalidomide p.o. 100 mg for 4 months, qn).

The following concomitant medications are not allowed during the study as they interfere with
Sponsor: Shanghai Jiao Tong University School of Medicine

Current Primary Outcome: Proportion of subjects whose bleeding episode decreased from baseline by ≥ 50% at 12 months follow-up after 4-month treatment [ Time Frame: 12 months ]

Proportion of subjects whose bleeding episode decreased from baseline by ≥ 50% at 12 months follow-up after 4-month treatment. The details are showed as follows: Reduction of bleeding episode = [(total bleeding episodes at 12 months - total bleeding episodes at a year before randomisation)/total bleeding episodes at a year before randomisation (baseline)]*100%. Rebleeding was defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change from baseline in bleeding episodes at 12 months [ Time Frame: baseline and 12 months ]
    Change from baseline in bleeding episodes at 12 months
  • Change from baseline in bleeding duration at 12 months [ Time Frame: baseline and 12 months ]
    Change from baseline in bleeding duration at 12 months
  • Change from baseline in proportion of subjects who dependent on blood transfusions at 12 months [ Time Frame: baseline and 12 months ]
    Change from baseline in proportion of subjects who dependent on blood transfusions at 12 months
  • Change from baseline in number of blood units transfused in subjects who dependent on blood transfusions at 12 months [ Time Frame: baseline and 12 months ]
    Change from baseline in number of blood units transfused in subjects who dependent on blood transfusions at 12 months
  • Change from baseline in average hemoglobin (Hb) level at 12 months [ Time Frame: baseline and 12 months ]
    Change from baseline in average hemoglobin (Hb) level at 12 months


Original Secondary Outcome: Same as current

Information By: Shanghai Jiao Tong University School of Medicine

Dates:
Date Received: April 26, 2016
Date Started: March 2010
Date Completion: September 2014
Last Updated: April 26, 2016
Last Verified: April 2016