Effect of Atenolol Versus Ivabradine on HRV in TRS Patients on Clozapine With Tachycardia: A Randomised Control Trial.
NCT Number: NCT06505668
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Treatment Resistant Schizophrenia|Clozapine Adverse Reaction|Heart Rate Variability|Tachycardia
Interventions: DRUG: Atenolol 25 mg|DRUG: Ivabradine 10mg
Sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sex: ALL
Age: ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: OTHER
Start Date: 2023-08-01
Completion Date: 2025-06-30
Locations: All India Institute of Medical Sciences, Bhubaneswar, Orissa, 751019, India

Summary:
Clozapine is the only drug approved for Treatment Resistant Schizophrenia. However, it has been associated with many adverse drug reactions including agranulocytosis, myocarditis, sialorrhea, constipation, orthostasis, tachycardia. There are many factors that have impacted the use of clozapine in TRS patients including physician hesitation, patient denial, stopping of drug due to Adverse drug reactions.

Although Tachycardia should not be the reason to stop clozapine, but data shows that it leads to discontinuation of drugs in significant patient population. If patient on clozapine develops tachycardia; first orthostasis, myocarditis and systemic infection should be ruled out. Tachycardia traditionally have been treated with B1 adrenergic blockers such as Atenolol. But the problem with beta blocker medications is that significant proportion develops hypotension.

Recently developed Ivabradine slows heart rate via I(f) current, and is not associated with much cardiac adverse effects. Recent Clinical trials have been carried out to show its effects on Clozapine associated tachycardia which shows promising results. Some studies suggest using Ivabradine in patient population that have contraindication for beta blockers.

Although both of these drugs are used widely in clinical practice, but as Ivabradine is relatively new drug there have been no head-to-head comparison with Atenolol. A recent meta-analysis tried to compare treatment efficacy in these patients, but found no studies that met their inclusion criteria. This current study attempts to make such comparison and guide further research.

Primary Outcome Measures: To compare the effect of Atenolol vs Ivabradine as changes in the Frequency domain of HRV over 2 months., Change in frequency domain parameters of participants will be compared between both the arms., 2 months
Secondary Outcome Measures: To compare the changes in the time domain of HRV between the groups., Change in the time domain parameters of participants will be compared between both the arms., 2 months|To compare the changes in central & peripheral BP and Pulse Rate between the groups., Change in the time domain parameters of participants will be compared between both the arms., 2 months|To find any correlation between the severity of PANSS with HRV at baseline., PANSS will be applied at the baseline and will be correlated with HRV parameters of all participants., single measure|To compare the treatment emergent adverse reaction over 2 months between the groups., All the participants will be kept in contact throughout the intervention period and will be screened for any adverse drug reaction., 2 months