NCT01396720

Impact of Citalopharm and Fluvoxamine on Platelet Response to Clopidogrel, a Randomized, Double-blind, Crossover Trial

Completed Phase 1 Last updated 26 January 2013

What this trial tests

Phase 1 trial testing fluvoxamine in Drug Interactions Between Clopidogrel and Serotonin Reuptake Inhibitors in 15 participants. Completed in 1 December 2012.

Timeline

1 September 2011

Primary endpoint
1 December 2012

1 December 2012

Quick facts

Lead sponsor	Hadassah Medical Organization
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	15
Start date	1 September 2011
Primary completion	1 December 2012
Estimated completion	1 December 2012

Drugs / interventions tested

• fluvoxamine (FLUVOXAMINE) — full drug profile →
• citalopharm — full drug profile →

Conditions studied

• Drug Interactions Between Clopidogrel and Serotonin Reuptake Inhibitors — all drugs for Drug Interactions Between Clopidogrel and Serotonin Reuptake Inhibitors →

Sponsor

Hadassah Medical Organization — full company profile →

Who can join

Adults 18 to 60, male only, with Drug Interactions Between Clopidogrel and Serotonin Reuptake Inhibitors. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Platelet reactivity in response to clopidogrel
  Time frame: 12 months
  We will assess response to clopidogrel by two methods: 1. % change in platelet aggregation using light transmission aggregometry with ADP as agonist. 2. % of change in VASP phosphorylation - measure of activation of the platelet P2Y12 receptor (targeted by clopidogrel). The response clopidogrel will be measured after administration of clopidogrel and after co-administration of clopidogrel and each

Sponsor's own description

Clopidogrel is a platelets inhibitor that is widely used particularly during and after acute coronary events and coronary interventions. Several studies have shown that some patients are resistant to clopidogrel. The resistance mechanism is not entirely clear, but at least in part it is related to interactions between medications. Clopidogrel is a pro-drug converted in vivo to its active metabolite by CYP2C19 and CYP3A in the liver. Consequently drugs that inhibit the CYP2C19 can affect the production of the active metabolite and cause "clopidogrel resistance". Therefore the FDA has recently published a "safety alert" which recommends avoiding cross treatment with clopidogrel and drugs that are expected to inhibit CYP2C19 (including omeprazole, fluvoxamine, cimetidine, fluconazole and others). Nevertheless there no clear evidence in the literature for clinical relevance of such interactions.

Selective serotonin reuptake inhibitors (SSRIs) are group of antidepressant drugs that are widely used for treatment of depression and anxiety. SSRIs are considered to be very safe with favorable side effect profile, hence many patient after coronary events who suffers from behavioral and emotional disturbances are treated with those drugs. However there are several reports that SSRIs can inhibit platelet function and increase bleeding tendency particularly in concomitant administration with aspirin. The proposed mechanism is blocking of platelets serotonin reuptake that result in platelet dysfunction.

Fluvoxamine - is a member in the SSRI family and a potent inhibitor of the CYP2C19. Theoretically fluvoxamine should have two conflicting effects on the response to clopidogrel. Pharmacokinetically it is expected to decrease the clopidogrel responsiveness due to inhibition of CYP2C19 and reduction in the production of the active metabolite. On the other hand "pharmacodynamically" fluvoxamine may directly inhibit platelet aggregation due its effect on serotonin reuptake, thus increasing the effect of clopidogrel. Other SSRIs that do not interact with the CYP2C19 such as citalophram are expected to have only pharmocodynamic effect on platelet aggregation.

Although both clopidogrel and SSRIs are widely used in the last decade and concomitant treatment is quite common, no data is available about in influence of the interaction between those drugs on platelet function and on clinical events. The net effect of fluvoxamine and other SSRIs on platelet function in the presence of clopidogrel is not known.

The aim of the investigators study is to assess the effect of two SSRIs fluvoxamine and citalophram on platelet aggregation and to test the effect of these drugs on the laboratory response to clopidogrel, in healthy individuals.

Study design: randomized, double blinded, controlled crossover trial. Primary study end point: Change in % platelet aggregation and VASP phosphorylation after treatment with clopidogrel + fluvoxamine or clopidogrel + citalophram as compared to each drug alone.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.