Deferoxamine and Xingnaojing Injection Treatment in Intracerebral Hemorrhage

May 14, 2015 updated by: Maolin He, Capital Medical University

Safety and Effectiveness Study of Deferoxamine and Xingnaojing Injection in Intracerebral Hemorrhage

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Research shows that more than 1/3 of patients with acute cerebral hemorrhage in the first 24 hours will be expanding hematoma. The treatment of acute cerebral hemorrhage has two main targets: prevention of hematoma enlargement in primary brain damage; Reduce hematoma secondary brain damage caused by blood toxicity degradation products. At present, the curative effect of drug treatment of acute cerebral hemorrhage remains limited, using drug therapy to treat hematoma caused by blood toxicity degradation products secondary brain damage, is one of the main current international research direction and hotspot. Recent studies have found that iron overload in cells in acute cerebral hemorrhage stove weeks edema secondary lesion plays a very important role. Acute cerebral hemorrhage animal model research and small sample clinical study has shown that the iron chelator deferoxamine has good curative effect and security. Currently ongoing international HI-DEF test plans to assess the efficacy and safety of high-dose deferoxamine treatment within 24 h of patients with acute cerebral hemorrhage.

Basic research shows Xingnaojing injection can inhibit inflammatory reaction, scavenging free radicals, relieve acute cerebral hemorrhage hematoma surrounding edema and has a variety of brain protection mechanism. The current study builds on these results to assess the potential utility of deferoxamine and Xingnaojing injection as a therapeutic intervention in ICH.

This is a prospective, multi-center, double-blind, randomized, placebo-armed clinical study to test the safety and effectiveness of deferoxamine and Xingnaojing injection treatment in intracerebral hemorrhage. The investigators will randomize 180 subjects with ICH equally (1:1:1) to either DFO at 40mg/kg/day (up to a maximum daily dose of 6000 mg/day), or Xingnaojing injection, or saline placebo, given by continuous IV infusion for 5 consecutive days. Treatment will be initiated within 12 hours after ICH symptom onset.

The main objectives are:

  1. Examining the effects of DFO and Xingnaojing injection on peri-hematoma edema (PHE) volume progression between baseline and post-treatment CT/MRI scans and the residual cavity volume at 90 days.
  2. Obtaining data on the National Institute of Health Stroke Scale (NIHSS) to explore the effects of treatment on neurological functions.
  3. Examining the effects of DFO and Xingnaojing injection on biomarkers of acute cerebral hemorrhage such as ferritin, interleukin - 6, matrix metalloproteinase 9, tumor necrosis factor alpha and so on.
  4. Study the traditional Chinese medicine(TCM)curative effect evaluation of the roles of different treatment methods on secondary damage after ICH.

Secondary and exploratory objectives include:

  1. Exploring whether the effect of DFO on outcome is dependent on initial ICH volume, after adjusting for other prognostic variables, to determine if specific limits for ICH volume should be specified as exclusion/inclusion criteria for future studies.
  2. Exploring the differences between early (≤12h) and late (>12-24h) OTT windows in DFO treatment effect on functional outcome.

Exploratory study shows that iron chelator deferoxamine is effective and safe in the treatment of acute cerebral hemorrhage. We choose within 12 hours as the treatment time window, different from within 24 hours in the current international ongoing HI-DEF test. In theory, the earlier, the better curative effect. So this experiment is more likely to get a better curative effect. Xingnaojing injection is widely used in clinical in china, but lack of rigorous randomized controlled trial to prove its brain protection effect currently. Successful completion of this study will provide a crucial, reliable experimental evidence for a new treatment for acute cerebral hemorrhage. ICH is one of main causes of disability and death. A successful study demonstrating the efficacy of DFO and xingnaojing injection would be of considerable public health significance.

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100038
        • Recruiting
        • Department of Neurology，Beijing Shijitan Hospital，Capital Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Known hypersensitivity to deferoxamine or xingnaojing injection
  2. Known severe iron deficiency anemia (defined as hemoglobin concentration < 7g/dL or requiring blood transfusions)
  3. Abnormal renal function, defined as serum creatinine > 2 mg/dL
  4. Planned surgical evacuation of ICH prior to administration of study drug
  5. Suspected secondary ICH related to tumour, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis
  6. Infratentorial hemorrhage
  7. Irreversibly impaired brainstem function (bilateral fixed and dilated pupils and extensor motor posturing)
  8. 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)
  9. Pre-existing disability, defined as pre-ICH mRS ≥ 2
  10. 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
  11. Taking iron supplements containing ≥ 325 mg of ferrous iron
  12. Patients with heart failure taking > 500 mg of vitamin C daily
  13. Known severe hearing loss
  14. Known pregnancy, or positive pregnancy test, or breastfeeding
  15. 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
  16. Life expectancy of less than 90 days due to comorbid conditions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Deferoxamine
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
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.
Other Names:
  • Deferoxamine Mesylate
Active Comparator: Xingnaojing injection
Xingnaojing injection supplied in vials containing 20 ml liquid xingnaojing.
Drug: Xingnaojing injection
Xingnaojing injection (20 ml/day) given by a continuous IV infusion for 5 consecutive days beginning within 12 hours of ICH symptom onset.
Placebo Comparator: Normal Saline
0.9% sodium chloride
Drug: Normal saline
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.
Other Names:
  • 0.90% Sodium Chloride Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numbers of patients with the perihematomal edema (PHE) volume variation.
Time Frame: 7 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The residual cavity volume
Time Frame: 90 days
the variation of residual cavity volume of
90 days
The variation of the mRS score and the Bathel Index
Time Frame: 90 days
the variation of mRS score and Bathel Index of different treated subjects from ICH onset to treatment time windows.
90 days
mortality
Time Frame: 90 days
the mortality of different treated subjects from ICH onset to treatment time windows.
90 days
Frequency of Treatment-related Adverse Events
Time Frame: 90 days
The safety endpoints will include all DFO-related adverse events until day-7 or discharge (whichever is earlier), and DFO-related SAEs and through day-90.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Capital Medical University

Collaborators

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

Investigators

  • Principal Investigator: Maolin He, MD, Department of Neurology，Beijing Shijitan Hospital，Capital Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

February 13, 2015

First Submitted That Met QC Criteria

February 19, 2015

First Posted (Estimate)

February 20, 2015

Study Record Updates

Last Update Posted (Estimate)

May 18, 2015

Last Update Submitted That Met QC Criteria

May 14, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MHe

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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