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Volume Kinetics for Starch Solution and Acetated Ringers

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ClinicalTrials.gov Identifier: NCT01195025
Recruitment Status : Completed
First Posted : September 3, 2010
Results First Posted : October 22, 2014
Last Update Posted : October 22, 2014
Sponsor:
Information provided by (Responsible Party):
Joachim Zdolsek, University Hospital, Linkoeping

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Blood Volume
Blood Coagulation
Interventions Drug: acetated Ringers
Drug: colloid
Drug: colloid+acetated Ringer
Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
Enrollment 10

Recruitment Details 10 Healthy male volunteers 18 to 50 years old
Pre-assignment Details Random crossover study, with at least one week between every study occasion.
Arm/Group Title A. Acetated Ringers, B.Colloid and C. Colloid+Acetated Ringers A. Colloid, B. Colloid+Acetated Ringers and C.Acetated Ringers A. Acetated Ringers, B. Colloid+Acetated Ringers and C.Colloid A.Colloid, B. Acetated Ringers and C. Colloid+Acetated Ringers A. Colloid+Acetated Ringers, B.Colloid and C. Acetated Ringers
Hide Arm/Group Description

First intervention: A. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected.

Washout >7 days

Second intervention: B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

Washout > 7 Days

Third intervention: C. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

First intervention: A. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

Washout >7 days

Second intervention: B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

Washout > 7 Days

Third intervention: C. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected

First intervention: A. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by 150 minutes of equilibration, when blood samples were collected

Washout >7 days

Second intervention: B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

Washout > 7 Days

Third intervention: C. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

First intervention: A. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

Washout >7 days

Second intervention: B. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected.

Washout > 7 Days

Third intervention: C. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

First intervention: A. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

Washout >7 days

Second intervention: B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

Washout > 7 Days

Third intervention: C. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected.

Period Title: First Intervention A
Started 2 3 2 2 1
Completed 2 3 2 2 1
Not Completed 0 0 0 0 0
Period Title: Second Intervention B
Started 2 3 2 2 1
Completed 2 3 2 2 1
Not Completed 0 0 0 0 0
Period Title: Third Intervention C
Started 2 3 2 2 1
Completed 2 3 2 2 1
Not Completed 0 0 0 0 0
Arm/Group Title Dilution Effects of iv Fluids
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Three experiments:

A. acetated Ringers 20 ml/kg bodyweight during 30 minutes B. Hydroxy ethyl starch (HES) 6% 10 mL/kg bodyweight during 30 min C. A combination of A and B. HES during 0-30 min and Ringer's during 105-135 minutes.

Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
<=18 years
0
   0.0%
Between 18 and 65 years
10
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
22  (3.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
0
   0.0%
Male
10
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Sweden Number Analyzed 10 participants
10
1.Primary Outcome
Title Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both.
Hide Description

volume kinetics: mathematical calculation from hemoglobin variations during and after an infusion.

Degree of plasma dilution depending on which solution(s) and how much solution is/are given.

Time Frame 420 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All the 10 participating subjects. Analysis studying the summary of each of the included infusion occasions. Only acetated Ringers, only colloid and finally a combination of colloid and acetated Ringers.

Each experiment generated one distribution volume. (In experiment C one for acetated Ringer's and one for Starch (HES 6%)).

Arm/Group Title Hydroxyethyl Starch, Ringers and a Combination of Both.
Hide Arm/Group Description:
A. acetated Ringers 20 ml/kg bodyweight during 30 minutes B. Hydroxyethyl starch (HES 6 %, 10 ml/kg bodyweight during 30 minutes. C. Hydroxyethyl starch (HES 6 %, 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes.
Overall Number of Participants Analyzed 10
Median (Inter-Quartile Range)
Unit of Measure: Litre
Distribution volume of Acetated Ringers
5.53
(4.25 to 7.31)
Distribution volume for HES 6%
2.94
(2.65 to 3.31)
Distribution vol for HES combined with Ringer's
3.12
(3.01 to 3.45)
Distribution vol for Ringers combined with HES
4
(3.05 to 4.82)
2.Primary Outcome
Title Elimination Half Life for Different Fluids Alone or When Combined
Hide Description Volume kinetic analyses of the dilution of hemoglobin for different infusion fluids alone or in combination.
Time Frame 420 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All the 10 participating subjects. Analysis studying the summary of each of the included infusion occasions. Only acetated Ringers, only colloid and finally a combination of colloid and acetated Ringers. Each experiment generated one elimination half-life (In experiment C one for acetated Ringer's and one for starch (HES 6%)).
Arm/Group Title Hydroxyethyl Starch, Ringers and a Combination of Both.
Hide Arm/Group Description:
A. acetated Ringers 20 ml/kg bodyweight during 30 minutes B. Hydroxyethyl starch (HES 6 %, 10 ml/kg bodyweight during 30 minutes. C. Hydroxyethyl starch (HES 6 %, 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes.
Overall Number of Participants Analyzed 10
Overall Number of Units Analyzed
Type of Units Analyzed: Infusion protocols
30
Median (Inter-Quartile Range)
Unit of Measure: Minutes
Elimination half life for Ringer's
88
(54 to 150)
Elimination half life for HES
116
(87 to 152)
Elimination half life for HES (+ Ringer's)
126
(75 to 150)
Elimination half life for Ringer's (+ HES)
497
(146 to 805)
3.Secondary Outcome
Title Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids
Time Frame 420 min
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The study was analysed per protocol and missing values were not replaced. All pairs of all collected data in one series of experiments. The number of analysed data points for each subject was in experiment A: 26, in experiment B: 32 and in experiment C: 42.
Arm/Group Title Venous Hemoglobin and Non-invasive Hemoglobin (SpHb)
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A comparison of all paired hemoglobin measurements (B-Hb and SpHb) during the experiments for all the 10 volunteers.

Relative difference(%) = (SpHb - Hb)/((Hb+SpHb)/2) x 100

Overall Number of Participants Analyzed 10
Overall Number of Units Analyzed
Type of Units Analyzed: Hemoglobin measurements (pairs)
956
Median (Inter-Quartile Range)
Unit of Measure: percentage of relative difference
Ringers acetate
-5.3
(-10.4 to 1.5)
HES 6%
0.0
(-6.8 to 4.6)
HES 6% + Ringers acetate
1.5
(-4.9 to 10.9)
4.Secondary Outcome
Title Accuracy of Noninvasive Haemoglobin Measurement by Pulse Oximetry, for Different Fluids (Start to End of Infusion)
Hide Description

Difference between true hemoglobin B-Hb and measured hemoglobin with pulseoximeter (SpHb)at the end of an infusion in relation to the initial measured values SpHb and B-Hb at the start of the infusion.

Relative difference (%) = (SpHb - Hb)/((Hb+SpHb)/2) x 100

Time Frame 30 min
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only the pure experiments were included in this analysis. The combined experiment is not included since infusions were performed in sequence, which made the comparison of the bias for the two different fluids irrelevant.
Arm/Group Title Colloid (Voluven), Acetated Ringers and a Combination of Both.
Hide Arm/Group Description:

A. acetated Ringers 20 ml/kg bodyweight during 30 minutes B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes

The combined experiment is not included since infusions were performed in sequence, which made the comparison of the bias for the two different fluids irrelevant.

Overall Number of Participants Analyzed 10
Overall Number of Units Analyzed
Type of Units Analyzed: SpHb - B-Hgb
20
Median (Inter-Quartile Range)
Unit of Measure: percentage of relative difference
Ringer's acetate
7
(2.5 to 11.1)
Hydroxy ethyl starch 6%
-4.3
(-7.2 to -0.9)
5.Secondary Outcome
Title Variation of Coagulation Factors and Plasma Proteins During and After Infusion of Crystalloid and Colloid Solutions.
Hide Description The investigators will measure a few markers of coagulation (fibrinogen, thrombocytes, D-Dimer, PK-INR, aPTT, and coagulation factor VII) as well as Cystatin C, serum albumine and hemoglobin and how the concentration of these vary with the different dilutions of blood during and after infusion of a colloid and/or a crystalloid solution.
Time Frame 420 minutes
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Colloid-, Acetated Ringers and Combined
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Voluven, acetated Ringers: Infusions at three different occasions separated by at least one week.

A. acetated Ringers 25 ml/kg bodyweight during 30 minutes B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes. C. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 15 ml/kg bodyweight during 30 minutes.

All-Cause Mortality
Colloid-, Acetated Ringers and Combined
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Colloid-, Acetated Ringers and Combined
Affected / at Risk (%)
Total   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Colloid-, Acetated Ringers and Combined
Affected / at Risk (%)
Total   0/10 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Joachim Zdolsek
Organization: University Hospital Linköping
Phone: +46101030000
Responsible Party: Joachim Zdolsek, University Hospital, Linkoeping
ClinicalTrials.gov Identifier: NCT01195025     History of Changes
Other Study ID Numbers: VkVR
First Submitted: August 31, 2010
First Posted: September 3, 2010
Results First Submitted: March 12, 2014
Results First Posted: October 22, 2014
Last Update Posted: October 22, 2014