Influence of Tocolytical Medications on Hemodynamics (Central and Peripheral) and Vascular Function in a Pilot Study to Determine the Design of the Final Study and the Final Study Itself

Pilot Study: A Dose-Response Finding Study of Ritodrine (Pre-Par®) to Find the Highest Well Tolerated Dose in Young, Healthy, Female Volunteers. To Find the Size-Order of the Hemodynamical Effects of Ritodrine (PrePar®) and Atosiban (Tractocile®) to Determine the Relevance of a PK/PD-Modelling in the Final Study. Final Study: Investigating the Influence of Tocolytical Medications: Ritodrine (PrePar®) and Atosiban (Tractocile®) at the Clinical Dose on the Hemodynamics and Arterial Function in Healthy Female Volunteers, Compared to Placebo During Continuous Intravenous Infusion.

This trial will consist of two parts:

A pilot study in a three-way cross over trial to determine the highest well tolerated dose of Ritodrine (Pre-Par®), the impact of Atosiban (Tractocile®) on the hemodynamics and hence the design of the final study.

The final study is planned as a three-way crossover trial to investigate and compare the cardiovascular effects of Ritodrine, Atosiban and placebo to relate those effects to the pharmacokinetics of Ritodrine and Atosiban (PK/PD modelling).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ritodrine; Drug: Atosiban; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • University Hospital Ghent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age between 20 and 40 years old;
• In good health, especially no cardiovascular diseases, obstructive lung diseases, chronic kidney diseases or diabetes mellitus.
• Using a proper anticonception method (orally, subcutaneously);
• A negative pregnancy test.

Exclusion Criteria:

• Intolerance of Ritodrine;
• On chronic medication, except oral and subcutaneous contraception
• History or present presentation of cardiac arrythmias;
• Risk of being pregnant or less than 6 months postpartum;
• Giving breastfeeding;
• Previous uteral surgery;
• Using an intra-uteral device (IUD);
• A severe addiction: nicotine (> 10 cigarettes/day), alcohol (> 3 units/day), caffeine (> 5 units/day) or any extralegally drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 3; Placebo	Drug: Placebo; Glucose 5%, IV
Experimental: 1; Ritodrine (Pre-Par)	Drug: Ritodrine; Ritodrine (Pre-Par), maximum 400 µg/minute, IV
Experimental: 2; Atosiban (Tractocile)	Drug: Atosiban; Atosiban (Tractocile), maximum 300 µg/minute, IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hemodynamical effects of Ritodrine and Atosiban in comparison of those of placebo.	240 minutes

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of the specific dosing levels of the medications on the level of arterial stiffness	240 minutes
Effect of the specific dosing levels of the medications on the effects of the peripheral pulse wave reflections on the central, systolic blood pressure	240 minutes
Effect of the specific dosing levels of the medications on the distensibility of the blood vessel wall	240 minutes
Effect of the specific dosing levels of the medications on the cardiac output and total peripheral resistance	240 minutes
Effect of the specific dosing levels of the medications on peripheral brachial, systolic and diastolic blood pressure	240 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Luc Van Bortel, MD, PhD, University Hospital, Ghent

Publications and helpful links

Helpful Links

• Website of the University Hospital Ghent

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: May 15, 2008
• First Submitted That Met QC Criteria: May 16, 2008
• First Posted (Estimate): May 19, 2008

Study Record Updates

• Last Update Posted (Estimate): April 20, 2009
• Last Update Submitted That Met QC Criteria: April 17, 2009
• Last Verified: April 1, 2009

More Information

Terms related to this study

• Keywords: Hemodynamics and arterial function of healthy females
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Hormone Antagonists; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Atosiban; Ritodrine
• Other Study ID Numbers: 2008/110