Efficacy Study of Thalidomide in Gastrointestinal Vascular Malformation Related Bleeding

NCT02754960 | Withdrawn Phase 2 DMC

• 1 other identifier: rjyyxhk57809
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Hemorrhage; Vascular Malformation

Keywords

Gastrointestinal bleeding; Vascular malformation; Angiodysplasia; Thalidomide

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects whose bleeding episode decreased from baseline by ≥ 50% at 12 months follow-up after 4-month treatment

  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.

  12 months

Secondary Outcomes (5)

• Change from baseline in bleeding episodes at 12 months

  baseline and 12 months

• Change from baseline in bleeding duration at 12 months

  baseline and 12 months

• Change from baseline in proportion of subjects who dependent on blood transfusions at 12 months

  baseline and 12 months

• Change from baseline in number of blood units transfused in subjects who dependent on blood transfusions at 12 months

  baseline and 12 months

• Change from baseline in average hemoglobin (Hb) level at 12 months

  baseline and 12 months

Study Arms (2)

Thalidomide group

ACTIVE COMPARATOR

Patients were randomly assigned to the thalidomide group and received 100 mg of thalidomide (Pharmaceutical Co., Ltd. of Chang Zhou, China) orally four times daily at 10 p.m. for four months.

Drug: Thalidomide

Placebo group

PLACEBO COMPARATOR

Patients were randomly assigned to the placebo group and received 100 mg of thalidomide placebo (Pharmaceutical Co., Ltd. of Chang Zhou, China) orally four times daily at 10 p.m. for four months.

Drug: Placebo

Interventions

Thalidomide DRUG

Interventions administered (dosage, 100mg; dosage form, 25mg; frequency of administration, 1 time daily at 10 p.m)

Also known as: Softenon

Thalidomide group

Placebo DRUG

Placebo administered (dosage, 100mg; dosage form, 25mg; frequency of administration, 1 time daily at 10 p.m)

Also known as: Thalidomide placebo

Placebo group

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 40-85 years; women were post-menopausal, post-tubal ligation, or on some form of birth control like long-term laying up contraceptive ring or using condom;
• History of at least six documented gastrointestinal bleeding episodes in the year prior to randomization, which were refractory or inaccessible to endoscopic therapy or surgical ectomy;
• Confirmed diagnosis of vascular malformation by esophagogastroduodenoscopy (EGD), capsule endoscope (CE), double-balloon endoscope (DBE), or colonoscopy, but no obvious infectious, neoplastic, or other specific diagnosis;
• Angiodysplasia at endoscopy characterized by focal or diffused venous/capillary lesions presenting as bright red ectatic vessels or pulsatile red protrusions, with surrounding venous dilatation or patchy erythema with or without oozing;

You may not qualify if:

• Less than 1 year of bleeding history;
• GI bleeding caused by Esophageal varices, Mallory Weiss syndrome, Zollinger-Ellison syndrome, Suspicion of gastric malignancy at baseline endoscopy, Post-Billroth-resection, Biliary disorders, Gastrointestinal tumors, Crohn's disease or Ulcerative colitis, Hemangioma or unknown source of GI bleeding;
• Bleeding that needs emergent endoscopic treatment or surgery;
• Any significant "alarm symptoms" within the past 6 months, such as, unintentional weight loss, signs of gastrointestinal bleeding more than 2 weeks prior to enrolment, jaundice, or any other sign indicating serious or malignant disease;
• Malignancy or clinically significant cardiovascular, pulmonary, renal, pancreatic, hepatic disease, cirrhotic or portal hypertension gastropathy, rheumatologic disorders, uncontrollable diabetes mellitus or hypertension as judged by the investigator;
• A history of severe bilateral peripheral neuropathy or seizure activity, thromboembolic disease;
• A history of treatment with any dose of systemic or oral topical corticosteroids or aspirin, NSAIDs, anti-platelet drugs, anticoagulants, or Chinese medications (with salicylates), gingko, or Echinacea, or other putative immunomodulators or anti-angiogenic agents;
• Haemorrhagic disorders, platelets\<100 x 109/ L, APTT\>1.5x upper limit of normal (ULN), or treatment with low-molecular weight heparin;
• Need for continuous concurrent therapy during the study period with NSAIDs, ASA (including low dose),Warfarin (including other Vit K antagonists), anti-platelet drugs, anticoagulants, mephenytoin, atazanavir or Chinese medications (with salicylates), gingko, or Echinacea, or other putative immunomodulators or anti-angiogenic agents;
• Pregnancy or lactation. Woman of child-bearing potential must be either non-pregnant or postmenopausal or must use a reliable form of contraception during the study period, as judged by the investigator;
• Allergy to study medications;
• Currently undergoing systemic cancer chemotherapy or receiving radiation or had underwent systemic cancer chemotherapy or received radiation treatment.
• Use of any other investigational compound or participation in another clinical trial within 30 days prior to start of study medication;
• Alcohol and/or drug abuse (addiction or drug dependence) or any condition associated with poor compliance, including expected non-cooperation, as judged by the investigator;
• Previous participation in the study;

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Gastroenterology department; Ren Ji Hospital

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (2)

• Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, Fox L, Chernoff M, Wu AW, MacPhail LA, Vasquez GJ, Wohl DA. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997 May 22;336(21):1487-93. doi: 10.1056/NEJM199705223362103.

  PMID: 9154767 BACKGROUND

• Bauditz J, Schachschal G, Wedel S, Lochs H. Thalidomide for treatment of severe intestinal bleeding. Gut. 2004 Apr;53(4):609-12. doi: 10.1136/gut.2003.029710.

  PMID: 15016759 BACKGROUND

Related Links

• Approved drug page at FDA's Drugs@FDA web site
• Protocol of previous open-label, randomised, iron-controlled study of long-term effects of thalidomide for recurrent gastrointestinal bleeding due to vascular malformation

MeSH Terms

Conditions

Gastrointestinal Hemorrhage; Vascular Malformations; Angiodysplasia

Interventions

Thalidomide

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Vascular Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Zhizheng Ge, Ph.D, MD.

  Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: the director of the endoscopy center

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: April 28, 2016
• Study Start: March 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: September 1, 2014
• Last Updated: April 28, 2016

Record last verified: 2016-04

Locations

CN (1)