Dr. Siwaporn Chankrachang
Chiangmai Hospital

Dr. Samart Nitinum
Kingmongkutla Hospital

Dr. Nijasri Suwanwela
Chulalongkorn Hospital

Dr. Sombat Mungtavepongsa
Thammasar Hospital

The registration in China was supported by the results obtained from initial double-blind control randomized studies performed in China from 1999 to 2001 on 605 ischemic stroke patients at restoration stage. These studies evidenced NeuroAiD’s efficacy to improve stroke patients’ ability to recover even when started several weeks after the stroke onset. Given its unique profile in attending stroke patients’ needs with a very safe profile, NeuroAiD™ presents a strong opportunity to fill a gap in stroke patients’ treatment in the West.

605 ischemic stroke patients at a late stage (14 days-2months after the stroke onset ) were enrolled in these studies: 201 patients for the first trial and 405 patients for the second one.
Efficacy was assessed after one month of treatment. As per most of stroke trials, they consisted of measuring functional outcomes (independence ) and neurological deficit with standard scales these scales are akin to the mRS (modified Rankin Score) and National Institute of Health Stroke Scale (NIHSS), the standard stroke scales used presently in stroke clinical research.
The meta-analysis of these two studies showed an odd ratio of 2.4 (p=0.007) of reaching independence as well as a further reduction of 25% of motor deficits for subjects receiving Neuroaid vs subjects from the control group. These results have been peer reviewed and published recently in Stroke – click here to read the full paper.

Below is an abstract of the scientific paper written after completion of studies, this paper has undergone peer-review process and will be published in the Cerebrovascular Disease Journal.

Abstract:

Background and Objective: Previous studies on Danqi Piantan Jiaonang (DPJ), a traditional Chinese medicine, in stroke patients showed promising results. Our aim was to determine the safety of DPJ in normal subjects and stroke patients through a series of studies assessing its immediate and long-term effects, alone and in combination with aspirin, on hematological, hemostatic, and biochemical parameters.

Methods: We conducted three studies from December 2004 to May 2006. Study I was a case series which recruited 32 healthy volunteers who were given two oral doses of four DPJ capsules (0.4g/ capsule) six hours apart. Study II was a randomized controlled trial of 22 healthy volunteers to receive either one oral dose of aspirin 300 mg alone or a combination of one dose of aspirin 300 mg and two doses of four DPJ capsules taken six hours apart. For both studies I and II, hemostatic parameters (PT, aPTT, Fibrinogen, platelet aggregation, D-Dimer) were tested at baseline, 2 hours, and 8 hours. Study III was a case series which recruited 10 patients with recent ischemic stroke (within 7 days) who were given four DPJ capsules taken orally three times a day for one month. Blood tests for hemostatic, hematological (complete blood count), and biochemical parameters (glucose, creatinine, ALT, AST, C-reative protein) were performed at baseline, 1 week, and 4 weeks.

Results: Apart from the expected changes in platelet aggregation in subjects taking aspirin, no significant differences were detected in hemostatic parameters at baseline, 2 hours, and 8 hours after oral intake of DPJ alone or in combination with aspirin. Likewise, no significant differences were observed in hematological, hemostatic, and biochemical parameters at baseline, 1 week, and 4 weeks of oral intake of DPJ.

Conclusion: Danqi Piantan Jiaonang (NeuroAiD®) does not significantly modify hematological, hemostatic, and biochemical parameters in normal subjects and stroke patients.

-          Neuroaid in Stroke Recovery – European Neurology

In order to determine the efficacy of Neuroaid when treatment is initiated within 72 hours of stroke[ e, CHIMES Society will support the expansion of Neuroaid in mainstream medicine practice implementing a randomized double blinded controlled clinical trial: CHInese Medicine Neuroaid Efficacy on Stroke recovery trial (CHIMES).

This study, performed following Western clinical trial standard methodology: it is a double blind randomized placebo controlled trial. in The trial has started in November 2007 and is now recruiting patients in several hospitals located in Singapore, Philippines and Thailand. CHIMES aims at completing patient inclusion in 2010.

CHIMES Society aims at measuring the efficacy of NeuroAiD using Western clinical trials methodology. Positive results from such a trial will establish clearly in western medicine the potential of NeuroAiD and support the awareness of such treatment’s availability in the medical and patient communities.

The goal of the trial is to test the hypothesis that NeuroAiD is superior to Placebo in reducing neurological deficit and improving functional outcome in patients with cerebral infarction with intermediate range of severity (6<14), recruited within 72 hours of the stroke onset.

This is a multi-center double blind controlled randomized trial comparing NeuroAiD versus a matched placebo assessing efficacy after three months of treatment.

The Study Endpoints are:

• Primary Efficacy Outcomes is the modified Rankin Scale grades at 3 months for all randomized subjects.
• Secondary Efficacy Outcomes are standard Western scales such as for stroke: NIHSS, mRS, Barthel index, mini-mental State Examination (MMSE).

Eligibility criteria have been chosen to allow most of the ischemic stroke patients to be included in the study and benefit from the TCM treatment.

Patient participation to the study will consist of a simple procedure:

• Recruitment: The investigator in charge of the trial determines whether the patient fits the criteria of inclusion and exclusion. Once eligibility is confirmed, the patient is offered to participate to the trial and is asked to sign a consent form.
• Assignment: The patient eligible is randomly assigned either to NeuroAiD or to a matched-placebo for 3 months.
• Initial assessment: On the first day of treatment, the doctors assess the patient neurological disability on 3 stroke standard scales used in western clinical trial methodology: NIHSS (neurological deficits), mRS (functional outcome) and MMSE (cognitive functions).
• Assessment at discharge from the hospital: When the patient leaves the hospital, the doctor will conduct a similar examination to assess the patient improvement.
• Assessment at 1 month: This assessment is performed by phone and assesses only patient autonomy (mRS).
• Assessment at 3 months: the patient recovery is assessed by investigators on the same three standards scales. Patient independence from any help, physical or verbal will also be measured by a fourth test called Barthel Index.

As per standard clinical trial guidelines, the CHIMES Society has appointed a Data and Safety Monitoring Board that will provide an unbiased process through which the CHIMES study will be monitored and patient safety protected.

Inclusion criteria
A subject will be eligible for inclusion in the trial only if all the following criteria apply at Baseline:

• Cerebral infarction of moderate severity
• Beginning of treatment within 72 hours after symptoms onset
• 18 years old and above
• No existing disability pre-stroke (mRS<1)
• Non childbearing potential for females

Exclusion criteria
A subject will not be eligible for inclusion in the trial if any of the following criteria apply at baseline:

• Evidence of other diagnosis (hemorrhage…)
• Patient benefiting from thrombolysis
• Known contra-indication for the use of all antiplatelet drugs
• Patient on anticoagulation therapy
• Co-existing systemic diseases (terminal cancer, renal failure cirrhosis, severe dementia or psychosis)
• Recent participation in another clinical trial within the last three months

The protocol is also available on www.ClinicalTrials.gov under the identifier NCT00554723.

Study Objective
To test the hypothesis that Neuroaid is superior to Placebo in reducing neurological deficit and improving functional outcome in patients with cerebral infarction of an intermediate range of severity (6 ≤ NIHSS ≤ 14).

Study Population
Potential subjects are screened for eligibility at baseline.

Inclusion criteria:
A subject will be eligible for inclusion in the trial only if all the following criteria apply at baseline:

• Subject is aged 18 years old and above
• Subject is on anti-platelet therapy
• Subject has a pre-stroke Modified Rankin Scale inferior or equal to 1
• A female subject is eligible to participate in the trial if she is of non childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal)
• Subjects or his/her legally acceptable representative is willing to provide written informed consent
• Subject has a cerebral infarction with compatible imaging using Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI)
• Time window is less than 72 hours after symptoms onset
• Subject has cerebral infarction with an intermediate severity range 6≤NIHSS≤14

Exclusion criteria:
A subject will not be eligible for inclusion in the trial if any of the following criteria apply at baseline:

• Subjects deemed unstable by investigator after thrombolysis treatment
• Subject has evidence of intra-cerebral hemorrhage on brain CT scan or MRI
• Subject has a rapidly improving neurological deficit
• Subject has definite indication for full-dose or long-term anticoagulation therapy
• Subject has other significant non-ischemic brain lesion which could affect function or disability
• Subject has co-existing systemic diseases which may affect assessment or follow-up such as terminal cancer, renal failure (creatinine >200umol/L if known), cirrhosis, severe dementia or psychosis.
• Subject has participated in another clinical trial within the last three months