Clinical Trial Results:
Influence of iodinated contrast agents on heart rate variation and diagnostic image quality during CT angiography of the coronary arteries
|
Summary
|
|
EudraCT number |
2011-001419-29 |
Trial protocol |
AT |
Global end of trial date |
31 Dec 2013
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
10 Jun 2021
|
First version publication date |
10 Jun 2021
|
Other versions |
|
Summary report(s) |
manuscript entire study |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
HRVCTA1
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Medical University Vienna
|
||
Sponsor organisation address |
Spitalgasse 23, Vienna, Austria, 1090
|
||
Public contact |
Division for Cardiovascular and Interventional Radiology, Department of Bioimaging and Image Guided Therapy, +43 14040058020, christian.loewe@meduniwien.ac.at
|
||
Scientific contact |
Division for Cardiovascular and Interventional Radiology, Department of Bioimaging and Image Guided Therapy, +43 14040058020, christian.loewe@meduniwien.ac.at
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
31 Dec 2018
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
30 Jun 2013
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
31 Dec 2013
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
• To demonstrate the possibility of reducing the heart rate changes during CT angiography of the coronary arteries by selecting an iso-osmolar contrast agent
|
||
Protection of trial subjects |
the entire study was approved by the institutional review board.
patient insureance: Zürich Versicherungs AG, Schwarzenbergplatz 15, A-1010 Vienna /Austria Nr. 07229622-2
patient related date pseudonymized
|
||
Background therapy |
patients referred to Cardiac CT for the suspicion for coronary artery disease have been randomized to undergo the CT examination using one out of two iodinated contrast agents. Both agents are well established and clinically approved, but have a different molecule structure. The influence on the heart rate change and variability during the CT examination and the possible difference between the two agents should be evaluated y careful assessment of the heart rate before, during and after the CT examination. Furthermore, a possible relation to the diagnostic image quality will be evaluated by blinded reading. | ||
Evidence for comparator |
Based on previously published data as well as based on unpublished data obtained at our own department there was some evidence of differences in the heart rate raise between the two contrast agents and a possible impact on diagnostic image quality. This was the motivation to perform this prospectively randomized trial. 1. Schroeder S, Kopp AF, Kuettner A, Burgstahler C, Herdeg C, Heuschmid M, Baumbach A, Claussen CD, Karsch KR, Seipel L. Influence of heart rate on vessel visibility in noninvasive coronary angiography using new multislice computed tomography: experience in 94 patients. Clin Imaging 2002;26(2):106-11 2. Svensson A, Ripsweden J, Ruck A, Aspelin P, Cederlund K, Brismar BT. Heart rate variability and heat sensation during CT coronary angiography: Low-osmolar versus iso-osmolar contrast media. Acta Radiol 2010;51(7):722-6. | ||
Actual start date of recruitment |
02 May 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Austria: 299
|
||
Worldwide total number of subjects |
299
|
||
EEA total number of subjects |
299
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
220
|
||
From 65 to 84 years |
77
|
||
85 years and over |
2
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
Patients referred for CCTA to rule out coronary artery disease (CAD) were invited to participate in this study. After an oral explanation of the content of the present study, written, informed consent was obtained from all patients. After obtaining consent, patients were randomized into two groups | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
The prerequisites for inclusion were age > 18 and presence of a sinus rhythm. Exclusion criteria: history of coronary stent placement, coronary bypass graft surgery or heart transplantation, history of multiple myeloma, impaired renal function (eGFR < 60 ml/min), untreated hyperthyreosis, as well as a history of allergic reaction to contrast media | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
overall trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
iodixanol | |||||||||
Arm description |
Patients referred to udnergo Cardiac CT were randomized and underwent the indicated Cardiac CT during the intravenous application of iodixanol | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Iodixanol
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Injection
|
|||||||||
Routes of administration |
Intravenous bolus use
|
|||||||||
Dosage and administration details |
Patients within both groups were subdivided according to their body weight into three body weight groups (<55 kg, 55 – 100 kg, >100 kg). Based on weight, the total amount of iodine was defined for each group, which determined the other parameters for contrast injection. The acquisition time, the injection duration, and thus, the injection speed, were defined, ensuring the same iodine delivery rate within every body weight class for both contrast agents (see Table 1). Patients who weighed below 55 kg received an iodine dose of 28 g, with a delivery rate of 1.76 g per second, patients between 55 kg and 100 kg received a total dose of 32 g, with a flow of 2 g per second, and patients above 100 kg received 36 g at a rate of 2.24 g per second.
|
|||||||||
|
Arm title
|
iomeprol | |||||||||
Arm description |
Patients referred for Cardiac CT were randoimzed and underwent the indicated examination during the intravenous administration of iomperol in this arm | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
iomeprol
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Infusion
|
|||||||||
Routes of administration |
Intravenous use
|
|||||||||
Dosage and administration details |
Patients within both groups were subdivided according to their body weight into three body weight groups (<55 kg, 55 – 100 kg, >100 kg). Based on weight, the total amount of iodine was defined for each group, which determined the other parameters for contrast injection. The acquisition time, the injection duration, and thus, the injection speed, were defined, ensuring the same iodine delivery rate within every body weight class for both contrast agents (see Table 1). Patients who weighed below 55 kg received an iodine dose of 28 g, with a delivery rate of 1.76 g per second, patients between 55 kg and 100 kg received a total dose of 32 g, with a flow of 2 g per second, and patients above 100 kg received 36 g at a rate of 2.24 g per second.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
overall trial
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
iodixanol
|
||
Reporting group description |
Patients referred to udnergo Cardiac CT were randomized and underwent the indicated Cardiac CT during the intravenous application of iodixanol | ||
Reporting group title |
iomeprol
|
||
Reporting group description |
Patients referred for Cardiac CT were randoimzed and underwent the indicated examination during the intravenous administration of iomperol in this arm | ||
|
|||||||||||||
End point title |
heart rate variation | ||||||||||||
End point description |
heart rate variation:
heart rate should be assessed at different time points (see also tabe 2) to allow for calculation of the heart rate variation:
baseline: heart rate 1 minute after Ca-scoring is defined as baseline heart rate (1 minute after Ca scoring, heart beats are counted for a time period of 30 seconds and are divided by 30 and multiplied by 60. This leads to baseline mean heart rate)
maximum/minimum heart rate: highest/lowest observed heart rate within 1 minute after start of contrast injection is defined as maximum/minimum heart rate
mean heart rate: mean heart rate within 1 minute after start of contrast injection is defined as mean heart rate (after start of contrast injection, heart beats are counted for a time period of 60 seconds)
heart rate variation: fluctuation from baseline is defined as heart rate variation (minimal and maximal heart rate during a time period of 1 minute are assessed and standard deviation from baseline is calculated)
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
60 sec after contrast injection
|
||||||||||||
|
|||||||||||||
Attachments |
heart rate variation |
||||||||||||
Statistical analysis title |
heart rate variation | ||||||||||||
Statistical analysis description |
The average heart rate (in bpm) of the initial measurement phase (60 seconds, before CA administration) was defined as the patient's resting heart rate (baseline). Heart rate changes after CA administration, defined as the deviations from the baseline, were determined once per second over a total of 50 seconds for each patient, and the two groups were then tested for significant differences.
|
||||||||||||
Comparison groups |
iodixanol v iomeprol
|
||||||||||||
Number of subjects included in analysis |
207
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence [1] | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
Mann-Whitney U | ||||||||||||
Confidence interval |
|||||||||||||
| Notes [1] - To evaluate changes in the variability of the RR interval duration during CA administration, two parameters were assessed: the standard deviation of all normal RR intervals (SDNN), which covers long-term RR variability; and the Root Mean Square of the Successive Differences (RMSSD), which covers short-term RR variability. |
|||||||||||||
|
|||||||||||||
End point title |
arterial contrast enhancement: | ||||||||||||
End point description |
The arterial enhancement in predefined vascular segments will be measured by one experienced technician.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
on the CT images, after acquisition
|
||||||||||||
|
|||||||||||||
Attachments |
table 3: HU, CNR and SNR |
||||||||||||
Statistical analysis title |
arterial enhancement | ||||||||||||
Statistical analysis description |
The HU values gathered for the four anatomical regions (left atrium, left ventricle, sinus valsalvae, and left main), as well as the calculated values for SNR and CNR, were tested for significant differences among the two CA groups using an unpaired t-test.
|
||||||||||||
Comparison groups |
iodixanol v iomeprol
|
||||||||||||
Number of subjects included in analysis |
207
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 1-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
overall image quality | ||||||||||||
End point description |
the overall subjective image quality will be assessed by two blinded readers in consensus according to the following five point scale:
0: not assessable
1: poor quality; more than 50% of segments not assessable
2: suboptimal quality, diagnosis hampered
3. good quality, diagnosis possible without major limitations
4. excellent quality; no limitations
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
assessment after image acquisition
|
||||||||||||
|
|||||||||||||
Attachments |
table 4 +5: image quality score |
||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||
End point title |
pateint discomfort | |||||||||
End point description |
the patient discomfort will be assessed after the end of heart beat measurements using a standardized visual assessment score (VAS, 0-10). Feeling of heat, cold, and pain at the injection site ranging from 0 = no pain to 10 = very severe pain will be assessed (attachement 1).
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
after image acquisition
|
|||||||||
|
||||||||||
Attachments |
figure 5 heat sensation |
|||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
safety / AE | |||||||||
End point description |
adverse events will be assessed up to 30 minutes after start of the contrast injection
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
0 - 30' after CT acquisition
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||
Timeframe for reporting adverse events |
0 - 30' after CT image acquisition similar as the normal clinical care
|
|||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||
Dictionary version |
22
|
|||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||
Reporting group title |
iodixanol
|
|||||||||||||||||||||
Reporting group description |
including all patients receiveing iodixanol as the contrast agent according to the randomization | |||||||||||||||||||||
Reporting group title |
iomeprol
|
|||||||||||||||||||||
Reporting group description |
including all patients receiveing iomeprol as the contrast agent according to the randomization | |||||||||||||||||||||
|
||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 3% | ||||||||||||||||||||||
|
||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
