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

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-60
SponsorAll India Institute of Medical Sciences, Bhubaneswar

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Atenolol 25 mg

    Drug

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

  • Ivabradine 10mg

    Drug

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

Treatment groups

40 Participants
are divided into 2 treatment groups
Group A: Atenolol 25mgActive comparator 1 intervention
Group B: Ivabradine 10mgActive comparator 1 intervention

Trial outcomes

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.

Time frame
2 months

Secondary outcomes

1

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.

Time frame
2 months
2

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.

Time frame
2 months
3

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.

Time frame
single measure
4

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.

Time frame
2 months

Other outcomes

Sponsors and contacts

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