Effect of Atenolol Versus Ivabradine on HRV in TRS Patients on Clozapine With Tachycardia: A Randomised Control Trial.

NCT06505668 | Recruiting

• 1 other identifier: AIIMSBBSR/PGThesis/2023-24/90
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Treatment Resistant Schizophrenia; Clozapine Adverse Reaction; Heart Rate Variability; Tachycardia

Keywords

Clozapine; Treatment resistant schizophrenia; heart rate variability

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• To compare the changes in the time domain of HRV between the groups.

  2 months

• To compare the changes in central & peripheral BP and Pulse Rate between the groups.

  2 months

• To find any correlation between the severity of PANSS with HRV at baseline.

  single measure

• To compare the treatment emergent adverse reaction over 2 months between the groups.

  2 months

Study Arms (2)

Atenolol 25mg

ACTIVE COMPARATOR

Patients will be receiving Atenolol 25mg OD for 2 months.

Drug: Atenolol 25 mg

Ivabradine 10mg

ACTIVE COMPARATOR

Patients will be receiving Ivabradine 10mg (5mg BD) for 2 months.

Drug: Ivabradine 10mg

Interventions

Atenolol 25 mg DRUG

Patients will be receiving Atenolol 25mg OD for 2 months.

Also known as: Arm A

Atenolol 25mg

Ivabradine 10mg DRUG

Patients will be receiving Ivabradine 5mg BD for 2 months.

Also known as: Arm B

Ivabradine 10mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All patients coming for treatment at the Out-patient department and In-patient department of the Department of Psychiatry fulfilling the following are included:
• Patients diagnosed with TRS (TRRIP consensus) receiving clozapine.
• Aged between 18 to 60 years of either sex
• Having baseline heart rate of \>100/minute.
• Written informed consent from Legally Authorized representative.

You may not qualify if:

• Patients with any one of the following are excluded from the study:
• Already receiving Atenolol or Ivabradine.
• Patients having any contraindication to using Atenolol or Ivabradine.
• Receiving any other medication other than Clozapine known to cause autonomic dysregulation.
• Active substance use.
• Serious medical or neurological comorbidity.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

All India Institute of Medical Sciences

Bhubaneswar, Odisha, 751019, India

RECRUITING

MeSH Terms

Conditions

Schizophrenia, Treatment-Resistant; Tachycardia

Interventions

Atenolol; Ivabradine

Condition Hierarchy (Ancestors)

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Biswa Ranjan Mishra, MD

  Professor and Head, Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Biswa R Mishra, MD, DPM

CONTACT

9438884220; brm1678@gmail.com

Amit Bahmnia, MBBS

CONTACT

9996445295; amitbahmnia@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head, Department of Psychiatry

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 17, 2024
• Study Start: August 1, 2023
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: July 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)