Assessment of efficacy and safety of Triflusal in ‘Aspirin Resistant’ patients with Type 2 Diabetes mellitus or documented Coronary Heart Disease (CHD)

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 To assess efficacy and safety of Triflusal in Aspirin resistant patients with Type 2 Diabetes mellitus or documented CHD

 Design

 Open labeled, prospective, single arm clinical study.

 Subject Selection

Number of Subjects:

 ·         40 patients who are Aspirin Resistant.

Inclusion Criteria

 Patients of any gender between 18 yrs and 65 yrs of age

Patients eligible for enrollment in the study must meet all the following criteria

 ·         Patients with Type 2 Diabetes mellitus or documented Coronary HeartDisease on a stable dose of Aspirin# and detected to be having Aspirin Resistance*.

 # Stable dose of Aspirin - Patient on Aspirin on a particular dosage for more than 7 days.

* Aspirin Resistance - Determined by increased Thromboxane B2 (TxB2) levels in urine using AspirinWorks®Test Kit.

 ·         Patients willing to provide informed consent and comply to the protocol.

 Exclusion Criteria

 Patients with any of the following criteria should not be enrolled in the clinical study:

 ·         Concomitant therapy with NSAIDs

·         History of active peptic ulcer

 Study Drug and Treatment

 ·         Tab. Triflusal 600 mg once daily for one month administered after food.

Study Plan

 Initial Screening

 ·         Patients with Type 2 Diabetes mellitus or documented CHD on a stable dose of Aspirin# would be screened for Aspirin Resistance* by measuring Thromboxane B2 (TxB2)levels in urine using AspirinWorks®Test Kit.

 ^ CHD risk equivalent considered as patients with Diabetes mellitus

 # Stable dose of Aspirin - Patient on Aspirin on a particular dosage for more than 7 days.

* Aspirin Resistance - Determined by increased Thromboxane B2 (TxB2)levels in urine using AspirinWorks®Test Kit.

 ·         These patient’s urine sample would be collected for analysis of baseline TxB2 levels

 o   Only in those patients with ’Aspirin Resistance’ (Determined by increased TxB2 levels), the urine sample would be further analyzed for baseline cyclic Adenosine Monophosphate (cAMP levels).

Treatment Phase

 ·         40 patients with proven ’Aspirin Resistance’ would be enrolled in the clinical study following fulfillment of the study criteria.

 o   This would be considered as ’Baseline visit’ wherein the patient consent would be taken for enrollment in the clinical study.

 o   Detailed history and examination of the patients will be done.

 o   Aspirin would be discontinued and initiated on Tablet Triflusal 600 mg once daily for a period of one month.

 ·         After one month of treatment with Triflusal (Final visit), patient would follow-up for reassessment. Patient’s Urine sample would be collected for analysis of TxB2 and cAMP levels.

 Assessment of Efficacy

Change inTxB2 and cAMP levels after one month of treatment with Triflusal 600mg OD in Aspirin Resistant patients.

·         Percentage decrease in TxB2 levels

·         Percentage increase in cAMP levels

Assessment of Safety

 At the Final Visit, the patient would be assessed for any adverse event that has occurred during the Treatment Phase.

Patient Withdrawal Criteria

Patient hospitalized due to cardiovascular disease or develops severe gastrointestinal hemorrhage at any point of time during the treatment phase – needs to be withdrawn from the study and treated as deemed appropriate.

Adverse Event

 Adverse event defined is: “Any untoward medical occurrence in a patient which does not necessarily have a causal relationship with this treatment”. This includes “any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the study drug”.

 At each visit, or study assessment, adverse events that might have occurred since the previous visit or assessment should be elicited from the patient and documented in the AE Initial Notification form.

 Sponsor would be responsible for following up with the investigator on predetermined intervals for any occurrence of adverse events.

 The causal relationship to be assessed by the investigator as:

1.      Probable = There is a reasonable causal relationship between the study drug and the AE. The event responds to dechallenge (withdrawal of study drug). Rechallenge is not required

2.      Possible = There is a reasonable causal relationship between the study drug and the AE. Dechallenge information (information referring to withdrawal of drug) is lacking or unclear

3.      Unrelated = There is not a temporal relationship to study drug administration (too early, too late, or study drug not taken), or there is a reasonable causal relationship between another drug, concurrent disease, or circumstance and the AE.

 Serious Adverse Event (SAE)

 The definition of Serious Adverse Event (SAE) is one that fulfils at least one of the following criteria:

 ·         Is fatal – results in death (NOTE: death is an outcome, not an event)

·         Is life-threatening.

·         Requires inpatient hospitalisation or prolongation of existing hospitalization.

·         Results in persistent or significant disability/incapacity

·         Is a congenital anomaly/birth defect

·         Jeopardized patient or required intervention

 Procedure for reporting of SAE

 All Serious adverse events must be reported within 24 hours by telephone (Tel. 022 40889083) or send the Adverse Event Initial Notification Form by Fax (022- 40888900) or e-mail: ae@glenmarkpharma.com