Deferoxamine and Xingnaojing Injection Treatment in Intracerebral Hemorrhage

Sponsor

Capital Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02367248

Collaborator

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

180

Enrollment

Location

Arms

21.1

Duration (Months)

8.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Intracerebral Hemorrhage	Drug: deferoxamine Drug: Xingnaojing injection Drug: Normal saline	Phase 1/Phase 2

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:

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.
Obtaining data on the National Institute of Health Stroke Scale (NIHSS) to explore the effects of treatment on neurological functions.
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.
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:

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.
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 Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

The residual cavity volume [90 days]
the variation of residual cavity volume of
The variation of the mRS score and the Bathel Index [90 days]
the variation of mRS score and Bathel Index of different treated subjects from ICH onset to treatment time windows.
mortality [90 days]
the mortality of different treated subjects from ICH onset to treatment time windows.
Frequency of Treatment-related Adverse Events [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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
Life expectancy of less than 90 days due to comorbid conditions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Neurology，Beijing Shijitan Hospital，Capital Medical University	Beijing		China	100038

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Maolin He, director of the Neurology department, Beijing Shijitan Hospital, Capital Medical University

ClinicalTrials.gov Identifier:

NCT02367248

Other Study ID Numbers:

First Posted:

Feb 20, 2015

Last Update Posted:

May 18, 2015

Last Verified:

May 1, 2015

Keywords provided by Maolin He, director of the Neurology department, Beijing Shijitan Hospital, Capital Medical University

Brain hemorrhage

Cerebral Hemorrhage

Deferoxamine

Xingnaojing injection

Hematoma edema

Additional relevant MeSH terms: