Trial Outcomes & Findings for Volume Kinetics for Starch Solution and Acetated Ringers (NCT NCT01195025)

NCT ID: NCT01195025

Last Updated: 2014-10-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

10 participants

Primary outcome timeframe

420 minutes

Results posted on

2014-10-22

Participant Flow

10 Healthy male volunteers 18 to 50 years old

Random crossover study, with at least one week between every study occasion.

Participant milestones

Participant milestones
Measure
A. Acetated Ringers, B.Colloid and C. Colloid+Acetated Ringers
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.
A. Colloid, B. Colloid+Acetated Ringers and C.Acetated Ringers
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
A. Acetated Ringers, B. Colloid+Acetated Ringers and C.Colloid
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.
A.Colloid, B. Acetated Ringers and C. Colloid+Acetated Ringers
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.
A. Colloid+Acetated Ringers, B.Colloid and C. Acetated Ringers
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.
First Intervention A
STARTED
2
3
2
2
1
First Intervention A
COMPLETED
2
3
2
2
1
First Intervention A
NOT COMPLETED
0
0
0
0
0
Second Intervention B
STARTED
2
3
2
2
1
Second Intervention B
COMPLETED
2
3
2
2
1
Second Intervention B
NOT COMPLETED
0
0
0
0
0
Third Intervention C
STARTED
2
3
2
2
1
Third Intervention C
COMPLETED
2
3
2
2
1
Third Intervention C
NOT COMPLETED
0
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Volume Kinetics for Starch Solution and Acetated Ringers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Dilution Effects of iv Fluids
n=10 Participants
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.
Age, Categorical
<=18 years
0 Participants
n=93 Participants
Age, Categorical
Between 18 and 65 years
10 Participants
n=93 Participants
Age, Categorical
>=65 years
0 Participants
n=93 Participants
Age, Continuous
22 years
STANDARD_DEVIATION 3.4 • n=93 Participants
Sex: Female, Male
Female
0 Participants
n=93 Participants
Sex: Female, Male
Male
10 Participants
n=93 Participants
Region of Enrollment
Sweden
10 participants
n=93 Participants

PRIMARY outcome

Timeframe: 420 minutes

Population: 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%)).

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.

Outcome measures

Outcome measures
Measure
Hydroxyethyl Starch, Ringers and a Combination of Both.
n=10 Participants
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.
Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both.
Distribution volume of Acetated Ringers
5.53 Litre
Interval 4.25 to 7.31
Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both.
Distribution volume for HES 6%
2.94 Litre
Interval 2.65 to 3.31
Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both.
Distribution vol for HES combined with Ringer's
3.12 Litre
Interval 3.01 to 3.45
Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both.
Distribution vol for Ringers combined with HES
4 Litre
Interval 3.05 to 4.82

PRIMARY outcome

Timeframe: 420 minutes

Population: 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%)).

Volume kinetic analyses of the dilution of hemoglobin for different infusion fluids alone or in combination.

Outcome measures

Outcome measures
Measure
Hydroxyethyl Starch, Ringers and a Combination of Both.
n=30 Infusion protocols
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.
Elimination Half Life for Different Fluids Alone or When Combined
Elimination half life for HES
116 Minutes
Interval 87.0 to 152.0
Elimination Half Life for Different Fluids Alone or When Combined
Elimination half life for Ringer's
88 Minutes
Interval 54.0 to 150.0
Elimination Half Life for Different Fluids Alone or When Combined
Elimination half life for HES (+ Ringer's)
126 Minutes
Interval 75.0 to 150.0
Elimination Half Life for Different Fluids Alone or When Combined
Elimination half life for Ringer's (+ HES)
497 Minutes
Interval 146.0 to 805.0

SECONDARY outcome

Timeframe: 420 min

Population: 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.

Pulse-oximeter based measurements compared with invasive hemoglobin measurements. All paired in the study. Accuracy depending on which infusion is selected (Ringer's, Hydroxyethyl starch or a combination of both).

Outcome measures

Outcome measures
Measure
Hydroxyethyl Starch, Ringers and a Combination of Both.
n=956 Hemoglobin measurements (pairs)
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.
Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids
Ringers acetate
-5.3 percentage of relative difference
Interval -10.4 to 1.5
Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids
HES 6%
0.0 percentage of relative difference
Interval -6.8 to 4.6
Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids
HES 6% + Ringers acetate
1.5 percentage of relative difference
Interval -4.9 to 10.9

SECONDARY outcome

Timeframe: 30 min

Population: 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.

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

Outcome measures

Outcome measures
Measure
Hydroxyethyl Starch, Ringers and a Combination of Both.
n=20 SpHb - B-Hgb
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.
Accuracy of Noninvasive Haemoglobin Measurement by Pulse Oximetry, for Different Fluids (Start to End of Infusion)
Ringer's acetate
7 percentage of relative difference
Interval 2.5 to 11.1
Accuracy of Noninvasive Haemoglobin Measurement by Pulse Oximetry, for Different Fluids (Start to End of Infusion)
Hydroxy ethyl starch 6%
-4.3 percentage of relative difference
Interval -7.2 to -0.9

SECONDARY outcome

Timeframe: 420 minutes

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.

Outcome measures

Outcome data not reported

Adverse Events

Colloid-, Acetated Ringers and Combined

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Joachim Zdolsek

University Hospital Linköping

Phone: +46101030000

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place