Retreatment and Its Efficiency of Thalidomide for Vascular Malformation Patients With Failure of First Course Treatment

NCT02301949 | Withdrawn Phase 2

• 1 other identifier: rjyyxhnj3015
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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 will perform a randomized, double blind, placebo controlled study of thalidomide as a retreatment therapy for recurrent gastrointestinal bleeding due to vascular malformation. Patients with failure of first course treatment of thalidomide will be randomly grouped, prescribed a second four-month course regimen of 25 mg of thalidomide or placebo orally four times daily. All patients will be monitored for at least one year. The primary end point is defined as the patients whose rebleeds decrease from baseline by ≥ 50% at 12 months and the cessation of bleeding. Rebleeding is defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment. Secondary outcomes include the participants dependent on blood transfusions and changes from baseline in transfused packed red cell units, bleeding episodes, and hemoglobin levels at 12 months. Statistical significance is defined at P \< 0.05.

Conditions

Gastrointestinal Bleeding of Unknown Origin; Gastrointestinal Vascular Malformation; Thalidomide Efficiency

Keywords

gastrointestinal bleeding; vascular malformation; thalidomide retreatment

Outcome Measures

Primary Outcomes (1)

• The primary end point is defined as the patients whose rebleeds decrease from baseline by ≥ 50% at 12 months

  The primary end point is defined as the patients whose rebleeds decrease 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 is 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 Hemoglobin (Hb) Level at 12 Months

  12 months

• Change From Baseline in Bleeding Episodes at 12 Months

  12 months

• Participants Dependent on Blood Transfusions

  12 months

• Change From Baseline in Total Transfused Red Cell Requirements at 12 Months

  12 months

• Cessation of Bleeding

  12 months

Study Arms (2)

Thalidomide Retreatment Group

ACTIVE COMPARATOR

Drug: Thalidomide

Placebo Group

PLACEBO COMPARATOR

Other: Placebo

Interventions

Thalidomide DRUG

Patients are randomly assigned to receive a second course of four-month treatment of thalidomide (Pharmaceutical Co., Ltd. of ChangZhou, China). Medications are taken orally 25mg four times daily at 6 a.m., 12 noon, 6 p.m., and 10 p.m.

Also known as: Softenon

Thalidomide Retreatment Group

Placebo OTHER

Patients are randomly assigned to receive placebo tablets (Pharmaceutical Co., Ltd. of ChangZhou, China) four times daily at 6 a.m., 12 noon, 6 p.m., and 10 p.m.

Placebo Group

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 35-85 years; women are post-menopausal, post-tubal ligation, or on some form of birth control like long-term laying up contraceptive ring or using condom;
• Patients with failure of first course treatment of thalidomide, which means rebleeds decreased from baseline by\< 50% at 12 months follow up ;
• History of at least six documented gastrointestinal bleeding episodes in the year prior first course thalidomide treatment, which are refractory or inaccessible to endoscopic therapy or surgical ectomy; so, patients should have at least four episodes of gastrointestinal bleeding a year prior our study;
• 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;
• Endoscopic appearance of GAVE (also known as watermelon stomach), indicated by longitudinal antral folds converging on the pylorus, containing visible columns of tortuous red ecstatic vessels.

You may not qualify if:

• Patients are excluded if first course treatment of thalidomide is effective, which means rebleeds decreased from baseline by ≥ 50% at 12 months follow up;
• if they have cirrhotic or portal hypertension gastropathy; severe co-morbidities of cardiac, pulmonary, renal, liver, hematological, rheumatologic disorders, or uncontrollable diabetes mellitus or hypertension;
• if they have a history of severe bilateral peripheral neuropathy or seizure activity, thromboembolic disease, known thalidomide allergy;
• if they have 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;
• Currently pregnant or lactating or currently undergoing systemic cancer chemotherapy or receiving radiation

Sponsors & Collaborators

• Zhizheng Ge: lead

Study Sites (1)

Department of Gastroenterology, Renji Hospital, Shanghai Institute of Digestive Diseases, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (4)

• 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

• Shurafa M, Kamboj G. Thalidomide for the treatment of bleeding angiodysplasias. Am J Gastroenterol. 2003 Jan;98(1):221-2. doi: 10.1111/j.1572-0241.2003.07201.x. No abstract available.

  PMID: 12526972 BACKGROUND

• Ge ZZ, Chen HM, Gao YJ, Liu WZ, Xu CH, Tan HH, Chen HY, Wei W, Fang JY, Xiao SD. Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation. Gastroenterology. 2011 Nov;141(5):1629-37.e1-4. doi: 10.1053/j.gastro.2011.07.018. Epub 2011 Jul 22.

  PMID: 21784047 BACKGROUND

MeSH Terms

Conditions

Gastrointestinal Hemorrhage; Vascular Malformations

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

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, MD. Ph.D

  Shanghai Ren Ji Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Shanghai Institute of Digestive Disease，Renji Hospital, Shanghai Jiao Tong University School of Medicine

Study Record Dates

• First Submitted: November 24, 2014
• First Posted: November 26, 2014
• Study Start: December 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2018
• Last Updated: April 21, 2016

Record last verified: 2016-04

Locations

CN (1)