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

Study Overview
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Brief Summary
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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).

Official Title
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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.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Ritodrine
* Drug: Atosiban
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodynamics and arterial function of healthy females