Efficacy and Safety of Qizhitongluo Capsule in the Recovery Phase of Ischemic Stroke

Efficacy and Safety of Qizhitongluo Capsule in the Recovery Phase of Ischemic Stroke With Qi Deficiency and Blood Stasis Syndrome: a Multicenter, Randomized,Double-blind，Placebo- and Active-controlled Adaptive Study

This is a 20-week study consisting of a 12-week multicenter, randomized,double-blind adaptive study to compare efficacy and safety of Qizhitongluo Capsule,Naoxintong Capsule and placebo in the recovery phase of ischemic stroke with qi deficiency and blood stasis syndrome, and a 8-week post-treatment safety follow-up.After 312 patients complete 12 weeks of treatment there will be an interim analysis.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: placebo; Drug: Qizhitongluo Capsule; Drug: Aspirin Enteric-coated Tablets; Behavioral: the routine recovery training; Drug: Naoxintong Capsule

• Study Type: Interventional
• Enrollment (Actual): 622
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100700
    • Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine
  • Beijing, China
    • Guang'anmen Hospital Nan District,China Academy of Chinese Medical Sciences
  • Tianjin, China
    • First Teaching Hospital of Tianjin University of TCM
  • Guangxi
    • Nanning, Guangxi, China, 530023
      • The First Affiliated Hospital of Guangxi University of Chinese Medicine
  • Hebei
    • Langfang, Hebei, China
      • Langfang TCM Hospital
  • Henan
    • Luohe, Henan, China, 462000
      • Luohe Hospital of Chinese Medicine
    • Zhengzhou, Henan, China
      • The first affiliated hospital of henan university of TCM
  • Jilin
    • Changchun, Jilin, China
      • The Affiliated Hospital To Changchun University of Chinese Medicine
  • Liaoning
    • Dalian, Liaoning, China
      • 201 Hospital of People's Liberation Army
    • Dalian, Liaoning, China
      • Zhongshan Hospital Dalian University
    • Shenyang, Liaoning, China
      • Second Hospital affiliated to Liaoning University of Traditional Chinese Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610075
      • Teaching Hospital of Chengdu University of Traditional Chinese Medicine
    • Chengdu, Sichuan, China
      • West China Hospital,Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age≥35 years and <80 years;
• Diagnosis of ischemic stroke in recovery phase, according to the Chinese guidelines for the diagnosis and treatment of acute ischemic stroke 2010;
• Diagnosis of ischemic stroke with qi deficiency and blood stasis syndrome;
• The interval from the onset to recruitment was 15-28 days;
• FM score <90 or AQ<93.8 and diagnosis of aphasia;
• Diagnosis of cerebral anterior circulation obstruction;
• 4≤ NIHSS score<20;
• Patient is willing to participate voluntarily and to sign a written patient informed consent.

Exclusion Criteria:

• Evidence of intracranial hemorrhage (ICH) or other cerebral diseases (eg.vascular malformation, tumor, abscess or multiple sclerosis etc.) on CT or MRI.
• Known history of allergy or suspected allergic to the study drugs.
• Liver function impairment with the value of ALT or AST over 1.5-fold of normal value.
• Renal dysfunction with the value of serum creatinine over 1.5-fold of normal value.
• Cerebral embolism caused by cerebral tumor, cerebral trauma, cerebral parasitosis, rheumatic heart disease, coronary heart disease or other cardiac diseases complicated with atrial fibrillation.
• Prestroke score on the mRS ≥2.
• Space-occupying lesions, CT or MRI revealed midline structure shift; CT revealed that massive cerebral infarction including more than one lobe of brain or over 1/3 of blood-supply area of middle cerebral artery.
• Disable patients prescribed by law（blind, deaf, dumb, mental retardation, mental disorders and physical disabilities which due to other causes affect neural function deficient scale).
• Hemorrhagic tendency or recent severe or dangerous bleeding in 3 months.
• Suspected addicted into alcohol or drug abuse; with severe complications that would make the condition more complicated assessed by the investigator.
• Woman with pregnancy, lactation or positive result of pregnancy test, or women who want to be pregnant in recent.
• Patient who is participating in other trials or has been participated in other trials in recent 3 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Qizhitongluo Capsule; Basic treatment：Aspirin Enteric-coated Tablets was administered orally at a dosage of 100mg/d once per night;the routine recovery training. intervention treatment:the Capsules were administered orally, four capsules each time, three times a day after each meal（placebo was taken only after lunch, and Qizhitongluo Capsule was taken after breakfast and supper)for 12 weeks.	Drug: placebo; Drug: Qizhitongluo Capsule; Other Names: QZTL group; Drug: Aspirin Enteric-coated Tablets; Behavioral: the routine recovery training
Active Comparator: Naoxintong Capsule; Basic treatment：Aspirin Enteric-coated Tablets was administered orally at a dosage of 100mg/d once per night; the routine recovery training. intervention treatment:Naoxintong Capsule was administered orally, four capsules each time, three times a day after each meal for 12 weeks.	Drug: Aspirin Enteric-coated Tablets; Behavioral: the routine recovery training; Drug: Naoxintong Capsule; Other Names: NXT group
Placebo Comparator: Placebo; Basic treatment：Aspirin Enteric-coated Tablets was administered orally at a dosage of 100mg/d once per night and the routine recovery training. intervention treatment:placebo capsule was administered orally four capsules each time, three times a day after each meal for 12 weeks.	Drug: placebo; Drug: Aspirin Enteric-coated Tablets; Behavioral: the routine recovery training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change in the Lower Extremity Fugl-Meyer score	baseline, after 4,12 weeks of treatment, after 90 days of onset.

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Aphasia Quotient（AQ) score	baseline, after 4,12 weeks of treatment, after 90 days of onset.
Change in Barthel Index score and proportion of subjects with Barthel Index score ≥90	baseline, after 4,12 weeks of treatment, after 90 days of onset.
Change in the Upper Extremity Fugl-Meyer score	baseline, after 4,12 weeks of treatment, after 90 days of onset.
Change in the total Fugl-Meyer motor score	baseline, after 4,12 weeks of treatment, after 90 days of onset.
Change in the syndrome score of Qi Deficiency and Blood Stasis	baseline, after 4,12 weeks of treatment, after 90 days of onset.
the incidence of New-onset cardiovascular events	during the 20-weeks
Changes in plasma glucose and lipid concentrations and blood coagulate	baseline and after 12 weeks of treatment
physical examination、 laboratory tests and ECG	baseline and after 12 weeks of treatment
the incidence of adverse events	during the 20-weeks
all cause mortality	during the 20-weeks

Other Outcome Measures

Outcome Measure	Time Frame
The modified Rankin Scale(mRS) score	baseline
the National Health Interview Surveys (NHISS) score	baseline

Collaborators and Investigators

• Sponsor: China Academy of Chinese Medical Sciences
• Investigators: Study Director: Zhong Wang, Ph.D., Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences; Principal Investigator: Yingzhen Xie, M.D., Dongzhimen Hospital, Beijing

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: January 4, 2013
• First Submitted That Met QC Criteria: January 4, 2013
• First Posted (Estimate): January 7, 2013

Study Record Updates

• Last Update Posted (Estimate): October 12, 2016
• Last Update Submitted That Met QC Criteria: October 11, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Ischemic Stroke,adaptive design, randomized, double-blind
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: QZTL2013; QZTL (Registry Identifier: QZTL)