A comparative study to evaluate the efficacy and safety of increasing Telmisartan dose versus adding Amlodipine in patients with stage 1 hypertension

Need for study: Hypertension (HTN) is the most common cardiovascular disease that affects about 1 billion individuals worldwide and 258 million individuals in India.  Recent global data on the diagnosis, treatment, and control rates of hypertension estimates that only 42% of people with hypertension are both diagnosed and treated pharmacologically, yet only 21% of people with hypertension have controlled blood pressure (BP). The clinical effects of poorly controlled hypertension are well‐established and results in hypertensive target organ damage such as cardiac disease, cerebrovascular disease, renal disease, and vascular disease.  Joint National Committee (JNC)-8, standard Guidelines for treatment and management of hypertension recommends to either initiate treatment with one drug, titrate to maximum dose and then add a second drug or to start one drug, then add a second drug before achieving maximum dose of first.  World Health Organization (WHO) Guidelines recommends to use fixed dose drug combinations of Calcium channel blockers (CCBs) and Angiotensin receptor blocker (ARB).  Telmisartan is a potent, long acting, non-peptide angiotensin II antagonist that acts on the angiotensin1(AT1) receptor subtype. CCBs are another class of first line anti-hypertensive drugs. Amlodipine, a third generation dihydropyridine calcium antagonist is illustrated by a lesser negative inotropic effect and higher vascular selectivity compared to other CCBs.  However, optimal treatment strategies in mild to moderate hypertension who fail to achieve blood pressure control with low dose monotherapy are not well established. This study is taken to compare which of the following guidelines has better efficacy in achieving blood pressure control by comparing high dose of Telmisartan versus low dose combination of Telmisartan and amlodipine. 

Objectives of the study:

• To evaluate the efficacy of increasing Telmisartan dose to 80mg versus adding Amlodipine 5mg in patients with stage 1 hypertension who did not respond to 4 weeks treatment with low dose Telmisartan of 40mg.

• To assess the safety of increasing Telmisartan dose to 80mg versus adding Amlodipine 5mg in patients with stage 1 hypertension who did not respond to 4 weeks treatment with low dose Telmisartan of 40mg.

Source of data: • Patients having uncontrolled blood pressure on low dose monotherapy with Telmisartan attending General Medicine Out Patient Department, Victoria Hospital, BMCRI.

Study design: Open label, comparative, non-randomized study.

Methodology: • After obtaining institutional ethics committee clearance and written informed consent , the out patients with stage 1 hypertension as diagnosed by physician fulfilling the inclusion/exclusion criteria will be enrolled for the study.

Reassessment of BP will be made by the physician based on two measurements of BP on two different occasions using auscultatory method after 10 minutes of rest.

The sphygmomanometer calibrated and BP will be recorded in right arm in sitting position with arm supported at heart level for every patient by same sphygmomanometer and by the same investigator.

According to treating physician choice the selected patients will be given either Telmisartan or Amlodipine and divided in to group A and group B respectively.

• Group-A: Patients (n= 40) to receive Telmisartan 80mg per day for 8 weeks.

• Group-B: Patients (n=40) to receive Telmisartan 40mg and Amlodipine 5 mg /day once daily for 8 weeks.

Demographic data, medical history, concomitant medications, physical examination, clinical examination, and details of drug prescription by the treating physician will be recorded in the case record form at baseline visit (visit 1/ day 1)

. Follow-up visits will be at 4th week (visit 2) and 8th week (visit 3) after administering the study drug.

A deviation of ±3 days for follow-ups will be accepted. Visit 1/ Day 1 baseline assessment -

• Patients will be given a thorough explanation of the study and written informed consent will be obtained.

• Patients will be enrolled as per inclusion/exclusion criteria.

• Details of patient’s demographic characteristics, medical history, concomitant medication, detailed physical/clinical examination including systolic/diastolic pressure will be recorded.

• Baseline readings of routine investigations such as Renal profile (Serum creatinine, Blood urea) and Serum Electrolytes will be recorded.

• Clear instructions regarding intake of study medication given to patient.

• Patient will be asked to return for follow up after 4 weeks.

Visit 2/ Week 4 -

• Systolic/diastolic BP with physical/clinical examination findings recorded.

• All observed or spontaneously reported adverse events will be recorded

• Patients will be asked to return for follow up after 4 weeks.

Visit 3/ Week 8 -

• Systolic/diastolic BP with physical/clinical examination findings recorded.

• All observed or spontaneously reported adverse events will be recorded.

• The routine investigations such as Renal profile (Serum creatinine, Blood urea) and Serum Electrolytes will be recorded.

• The study termination form will be completed.

Assessment Tools:

1. Efficacy assessed by – Measurement of BP.

2. Safety assessed by – number and severity of adverse events reported by the patient.

STATISTICAL ANALYSIS: The data collected will be analysed statistically using statistics namely mean, standard deviation, percentage wherever applicable. Results will be expressed as mean (SD). Group differences will be ascertained by unpaired t test. Difference within group will compared by repeated measures ANOVA. Categorical data will be assessed by Chi square test. The results will be considered statistically significant at p < 0.05.