Deferoxamine and Xingnaojing Injection Treatment in Intracerebral Hemorrhage

NCT02367248 | Unknown Phase 1 DMC

• 1 other identifier: MHe
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to determine whether deferoxamine and xingnaojing injection is effective and safe as a treatment for intracerebral hemorrhage.

Conditions

Intracerebral Hemorrhage

Keywords

Brain hemorrhage; Cerebral Hemorrhage; Deferoxamine; Xingnaojing injection; Hematoma edema

Outcome Measures

Primary Outcomes (1)

• Numbers of patients with the perihematomal edema (PHE) volume variation.

  decreases of more than 20% from initial PHE volumes were defined as "decreased" PHE volume; increases of more than 20% from initial PHE volumes were defined as "increased" PHE volume; changes between -20% and 20% were defined as "unchanged".

  7 days

Secondary Outcomes (4)

• The residual cavity volume

  90 days

• The variation of the mRS score and the Bathel Index

  90 days

• mortality

  90 days

• Frequency of Treatment-related Adverse Events

  90 days

Study Arms (3)

Deferoxamine

ACTIVE COMPARATOR

Deferoxamine mesylate supplied in vials containing 500 mg of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water.

Drug: deferoxamine

Xingnaojing injection

ACTIVE COMPARATOR

Xingnaojing injection supplied in vials containing 20 ml liquid xingnaojing.

Drug: Xingnaojing injection

Normal Saline

PLACEBO COMPARATOR

0.9% sodium chloride

Drug: Normal saline

Interventions

deferoxamine DRUG

Deferoxamine mesylate(40 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 12 hours of ICH symptom onset.

Also known as: Deferoxamine Mesylate

Deferoxamine

Xingnaojing injection DRUG

Xingnaojing injection (20 ml/day) given by a continuous IV infusion for 5 consecutive days beginning within 12 hours of ICH symptom onset.

Xingnaojing injection

Normal saline DRUG

This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 12 hours of ICH symptom onset.

Also known as: 0.90% Sodium Chloride Solution

Normal Saline

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 and ≤ 80 years
• The diagnosis of ICH is confirmed by brain CT scan
• NIHSS score ≥ 6 and GCS \> 6 upon presentation
• The first dose of the study drug can be administered within 12h of ICH symptom onset
• Functional independence prior to ICH, defined as pre-ICH mRS ≤ 1
• Signed and dated informed consent is obtained.

You may not qualify if:

• Known hypersensitivity to deferoxamine or xingnaojing injection
• Known severe iron deficiency anemia (defined as hemoglobin concentration \< 7g/dL or requiring blood transfusions)
• Abnormal renal function, defined as serum creatinine \> 2 mg/dL
• Planned surgical evacuation of ICH prior to administration of study drug
• Suspected secondary ICH related to tumour, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis
• Infratentorial hemorrhage
• Irreversibly impaired brainstem function (bilateral fixed and dilated pupils and extensor motor posturing)
• Complete unconsciousness, defined as a score of 3 on item 1a of the NIHSS (Responds only with reflex motor or autonomic effects or totally unresponsive, and flaccid)
• Pre-existing disability, defined as pre-ICH mRS ≥ 2
• Coagulopathy - defined as elevated aPTT or INR \>1.3 upon presentation; concurrent use of direct thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such as rivaroxaban), or low-molecular-weight heparin
• Taking iron supplements containing ≥ 325 mg of ferrous iron
• Patients with heart failure taking \> 500 mg of vitamin C daily
• Known severe hearing loss
• Known pregnancy, or positive pregnancy test, or breastfeeding
• Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, noncompliance, living in another state or any other cause

Sponsors & Collaborators

• Capital Medical University: lead
• Beijing Tiantan Hospital: collaborator
• Peking University First Hospital: collaborator
• People's Hospital of Beijing Daxing District: collaborator
• Beijing Haidian Hospital: collaborator
• The 263 Hospital of PLA: collaborator
• Beijing Aerospace General Hospital: collaborator
• Peking University Third Hospital: collaborator
• Beijing Pinggu District Hospital: collaborator
• Beijing Shuyi Hospital: collaborator
• General Hospital of Beijing PLA Military Region: collaborator
• Beijing Luhe Hospital: collaborator
• Beijing Fangshan District Liangxiang Hospital: collaborator
• Beijing Neurosurgical Institute: collaborator
• Beijing Jishuitan Hospital: collaborator
• Beijing Ditan Hospital: collaborator
• Beijing Youyi Hospital: collaborator
• Xiyuan Hospital of China Academy of Chinese Medical Sciences: collaborator
• Peking University People's Hospital: collaborator
• The Second Artillery General Hospital: collaborator
• Chinese PLA General Hospital: collaborator

Study Sites (1)

Department of Neurology，Beijing Shijitan Hospital，Capital Medical University

Beijing, 100038, China

RECRUITING

Related Publications (8)

• Okauchi M, Hua Y, Keep RF, Morgenstern LB, Schallert T, Xi G. Deferoxamine treatment for intracerebral hemorrhage in aged rats: therapeutic time window and optimal duration. Stroke. 2010 Feb;41(2):375-82. doi: 10.1161/STROKEAHA.109.569830. Epub 2009 Dec 31.

  PMID: 20044521 BACKGROUND

• Selim M. Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke. 2009 Mar;40(3 Suppl):S90-1. doi: 10.1161/STROKEAHA.108.533125. Epub 2008 Dec 8.

  PMID: 19064798 BACKGROUND

• Selim M, Yeatts S, Goldstein JN, Gomes J, Greenberg S, Morgenstern LB, Schlaug G, Torbey M, Waldman B, Xi G, Palesch Y; Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011 Nov;42(11):3067-74. doi: 10.1161/STROKEAHA.111.617589. Epub 2011 Aug 25.

  PMID: 21868742 BACKGROUND

• Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick JP, Connolly ES Jr, Greenberg SM, Huang JN, MacDonald RL, Messe SR, Mitchell PH, Selim M, Tamargo RJ; American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010 Sep;41(9):2108-29. doi: 10.1161/STR.0b013e3181ec611b. Epub 2010 Jul 22.

  PMID: 20651276 BACKGROUND

• Chaudhary N, Gemmete JJ, Thompson BG, Xi G, Pandey AS. Iron--potential therapeutic target in hemorrhagic stroke. World Neurosurg. 2013 Jan;79(1):7-9. doi: 10.1016/j.wneu.2012.11.048. Epub 2012 Nov 19. No abstract available.

  PMID: 23174156 BACKGROUND

• Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, Molina CA, Blas YS, Dzialowski I, Kobayashi A, Boulanger JM, Lum C, Gubitz G, Padma V, Roy J, Kase CS, Kosior J, Bhatia R, Tymchuk S, Subramaniam S, Gladstone DJ, Hill MD, Aviv RI; PREDICT/Sunnybrook ICH CTA study group. Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol. 2012 Apr;11(4):307-14. doi: 10.1016/S1474-4422(12)70038-8. Epub 2012 Mar 8.

  PMID: 22405630 BACKGROUND

• Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G. Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke. 2009 Jun;40(6):2241-3. doi: 10.1161/STROKEAHA.108.539536. Epub 2009 Apr 16.

  PMID: 19372448 BACKGROUND

• Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G. Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke. 2009 May;40(5):1858-63. doi: 10.1161/STROKEAHA.108.535765. Epub 2009 Mar 12.

  PMID: 19286595 BACKGROUND

MeSH Terms

Conditions

Cerebral Hemorrhage; Intracranial Hemorrhages

Interventions

Deferoxamine; xingnaojing; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Maolin He, MD

  Department of Neurology，Beijing Shijitan Hospital，Capital Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maolin He, MD

CONTACT

0086-010-63926550; maolinh@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director of the Neurology department, Beijing Shijitan Hospital

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 20, 2015
• Study Start: March 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 18, 2015

Record last verified: 2015-05

Locations

CN (1)