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Colchicine in Postoperative Fontan Patients (CPFP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03575572
Recruitment Status : Terminated (Staffing changes impacted by COVID-19 pandemic resulting in inadequate personnel to facilitate study.)
First Posted : July 2, 2018
Results First Posted : May 9, 2022
Last Update Posted : May 9, 2022
Sponsor:
Information provided by (Responsible Party):
Stephanie Goldstein, University of Michigan

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Single-ventricle
Heart Diseases
Intervention Drug: Colchicine
Enrollment 11
Recruitment Details  
Pre-assignment Details 2 people who were consented didn't actually begin the trial. Under the protocol, historical controls were not considered enrolled in this study, so they are not included in participant flow. Historical control data were taken from an observational study with no intervention that was published prior to first enrollment in this trial. Data on the historical controls are available at PMID: 30710164.
Arm/Group Title Colchicine
Hide Arm/Group Description All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.
Period Title: Overall Study
Started [1] 9
Completed 5
Not Completed 4
Reason Not Completed
Withdrawal by Subject             2
Physician Decision             2
[1]
Started is defined here to mean first sample collected.
Arm/Group Title Colchicine Historical Controls Total
Hide Arm/Group Description All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks. Historical Controls were post-operative Fontan patients who underwent their operation at the University of Michigan. They were part of a prospective observational study that was published in 2019 which included the chest tube drainage sample collection similar to that done with the Colchicine cohort in this trial. Total of all reporting groups
Overall Number of Baseline Participants 9 25 34
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 9 participants 25 participants 34 participants
2.7
(2.1 to 4.3)
2.5
(2.1 to 2.9)
NA [1] 
(NA to NA)
[1]
Complete historical control age data is no longer available. So, while median (2.5) and Inter-Quartile Range (2.1 to 2.9) is available for historical controls from previously published data, it is not possible to submit the results without the full population median and inter-quartile range computed. The full data set for the historical controls is not available to recompute the medians and IQR for the two populations combined.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 25 participants 34 participants
Female
5
  55.6%
7
  28.0%
12
  35.3%
Male
4
  44.4%
18
  72.0%
22
  64.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 25 participants 34 participants
American Indian or Alaska Native
1
  11.1%
0
   0.0%
1
   2.9%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  11.1%
0
   0.0%
1
   2.9%
White
6
  66.7%
22
  88.0%
28
  82.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
  11.1%
3
  12.0%
4
  11.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 9 participants 25 participants 34 participants
9 25 34
Primary Diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 25 participants 34 participants
Hypoplastic left heart syndrome (HLHS) 6 14 20
Not HLHS 3 11 14
1.Primary Outcome
Title Change in Cytokine Total Mass in Pleural Fluid From Patients Treated With Colchicine
Hide Description Cytokine total mass measured by the Bio-rad Bio-Plex ProHuman Cytokine 17-plex Assay.
Time Frame Postoperative day 1 ; day most distal from surgery, approximately 7 days after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Colchicine Per Protocol
Hide Arm/Group Description:

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These participants completed the protocol.

Overall Number of Participants Analyzed 5
Median (Inter-Quartile Range)
Unit of Measure: picograms
Interleukin (IL)-8; post op. Day 1
60925.8
(27396.7 to 123151.56)
IL-8, Day 7
8684.57
(2346.135 to 19715.275)
Tumor Necrosis Factor (TNF)-alpha, Day 1
6552.7
(4954.770 to 7482.8)
TNF-alpha, Day 7
694.575
(479.288 to 909.863)
Macrophage Inflammatory Protein (MIP)-1 Beta Day 1
4949.89
(4450.56 to 13543.4)
MIP-1 Beta Day 7
247.775
(225.088 to 270.463)
Interleukin (IL)-10 Day 1
5286.55
(4560.4 to 9763.27)
IL-10 Day 7
132.755
(117.558 to 147.953)
2.Primary Outcome
Title Difference in Change of Cytokine Concentrations in Pleural Fluid Patients Treated With Colchicine Compared to Historical Controls
Hide Description Difference is shown via two columns of separate data, but given that enrollment didn't meet target before termination statistical analysis was not done for this measure
Time Frame Postoperative day 1 ; day most distal from surgery, approximately 7 days after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Colchicine Historical Controls
Hide Arm/Group Description:

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These participants completed the protocol.

Historical Controls were post-operative Fontan patients who underwent their operation at the University of Michigan. They were part of a prospective observational study that was published in 2019 which included the chest tube drainage sample collection similar to that done with the Colchicine cohort in this trial.
Overall Number of Participants Analyzed 5 25
Median (Inter-Quartile Range)
Unit of Measure: picograms
IL-8 Day 1
60925.80
(27396.70 to 123151.56)
83263.45
(42239.05 to 369274.25)
IL-8 Day 7
8684.57
(2346.14 to 19715.28)
64695.50
(28829.240 to 253569.74)
TNF-Alpha Day 1
6552.70
(4954.77 to 7482.80)
8080.38
(6269.6 to 11148.0)
TNF-ALpha Day 7
694.575
(479.288 to 909.863)
3320.97
(1872.72 to 5481.28)
MIP-1 Beta Day 1
4949.89
(4450.56 to 13543.40)
11527.80
(6800.60 to 18611.90)
MIP-1Beta Day 7
247.775
(225.088 to 270.463)
5986.4
(3251.41 to 12216.24)
IL-10, Day 1
5286.55
(4560.4 to 9763.27)
14474.4
(8099.82 to 25592.7)
IL-10, Day 7
132.755
(117.558 to 147.953)
885.04
(693.12 to 1665.66)
3.Secondary Outcome
Title Cytokine Total Mass as Measured in Postoperative Fontan Patients Treated Empirically With Colchicine
Hide Description

Particularly Cytokine total mass of TNF-α, MIP-1β, IL-8, and IL-10, determined by the Bio-rad Bio-Plex ProHuman Cytokine 17-plex Assay

Data was only collected while patients had chest tubes in place (up to 7 days only)

Time Frame Postoperative days 1, 2, 3, 4, 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Colchicine Per Protocol
Hide Arm/Group Description:

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These participants completed the protocol.

Overall Number of Participants Analyzed 5
Median (Inter-Quartile Range)
Unit of Measure: picograms
IL-8 Day 1
60925.80
(27396.70 to 123151.56)
IL 8 Day 2
22178.00
(11356.16 to 57721.6)
IL 8 Day 3
26837.20
(15517.8 to 80660.56)
IL 8 Day 4
50895.36
(17402.06 to 113591.7)
IL 8 Day 7
8684.57
(2346.14 to 19715.28)
IL 10 Day 1
5286.55
(4560.40 to 9763.27)
IL 10 Day 2
2788.44
(2194.92 to 3084.90)
IL 10 Day 3
586.50
(401.60 to 1033.60)
IL 10 Day 4
448.06
(318.24 to 593.46)
IL 10 Day 7
132.755
(117.558 to 147.953)
TNF Alpha Day 1
6552.70
(4954.77 to 7482.80)
TNF Alpha Day 2
6220.50
(2854.30 to 6932.60)
TNF Alpha Day 3
3791.84
(2108.68 to 4360.80)
TNF Alpha Day 4
2517.90
(1248.72 to 2950.66)
TNF Alpha Day 7
694.575
(479.288 to 909.863)
MIP-1 Beta Day 1
4949.89
(4450.56 to 13543.40)
MIP-1 Beta Day 2
3066.80
(2566.10 to 10702.90)
MIP-1 Beta Day 3
4031.04
(2107.66 to 6968.00)
MIP-1 Beta Day 4
2730.50
(2327.64 to 5768.16)
MIP-1 Beta Day 7
247.775
(225.088 to 270.463)
4.Secondary Outcome
Title Difference in Cytokine Total Mass, as Measured in Postoperative Fontan Patients Treated Empirically With Colchicine in Comparison to a Cohort of Postoperative Fontan Patients
Hide Description

Cytokine total mass measured by Bio-rad Bio-Plex ProHuman Cytokine 17-plex Assay

Data was only collected from Colchicine patients while they had chest tubes in place (up to 7 days). For historical controls data was collected up through Day 10

Time Frame Postoperative days 1, 2, 3, 4, 7, 10
Hide Outcome Measure Data
Hide Analysis Population Description
Day 10 data was not gathered from participants per protocol, but it was available for historical controls.
Arm/Group Title Colchicine Per Protocol Historical Controls
Hide Arm/Group Description:

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These participants completed the protocol.

Historical Controls were post-operative Fontan patients who underwent their operation at the University of Michigan. They were part of a prospective observational study that was published in 2019 which included the chest tube drainage sample collection similar to that done with the Colchicine cohort in this trial.
Overall Number of Participants Analyzed 5 25
Median (Inter-Quartile Range)
Unit of Measure: picograms
IL-8 Day 1 Number Analyzed 5 participants 25 participants
60925.80
(27396.70 to 123151.56)
83263.45
(42239.05 to 369274.25)
IL-8 Day 2 Number Analyzed 5 participants 25 participants
22178.00
(11356.16 to 57721.6)
50734.56
(20064.46 to 177356.64)
IL-8 Day 3 Number Analyzed 5 participants 25 participants
26837.20
(15517.80 to 80660.56)
36175.15
(14641.888 to 95957.95)
IL-8 Day 4 Number Analyzed 5 participants 25 participants
50895.36
(17402.06 to 113591.7)
52203.825
(21544.800 to 142966.54)
IL-8 Day 7 Number Analyzed 5 participants 25 participants
8684.57
(2346.14 to 19715.28)
64695.5
(28829.24 to 253569.74)
IL-8 Day 10 Number Analyzed 0 participants 25 participants
140165.900
(28829.240 to 253569.740)
IL-10 Day 1 Number Analyzed 5 participants 25 participants
5286.55
(4560.4 to 9763.27)
14474.4
(8099.82 to 25592.7)
IL-10 Day 2 Number Analyzed 5 participants 25 participants
2788.440
(2194.92 to 3084.90)
5341.80
(2882.88 to 9084.43)
IL-10 Day 3 Number Analyzed 5 participants 25 participants
586.59
(401.60 to 1033.60)
1192.29
(914.91 to 3959.96)
IL-10 Day 4 Number Analyzed 5 participants 25 participants
448.06
(318.24 to 593.46)
1462.22
(645.84 to 2533.72)
IL-10 Day 7 Number Analyzed 5 participants 25 participants
132.755
(117.558 to 147.953)
885.04
(693.12 to 1665.66)
IL-10 Day 10 Number Analyzed 0 participants 25 participants
417.80
(397.70 to 879.52)
TNF Alpha Day 1 Number Analyzed 5 participants 25 participants
6552.70
(4954.77 to 7482.80)
8080.38
(6269.60 to 11148.00)
TNF Alpha Day 2 Number Analyzed 5 participants 25 participants
6220.50
(2854.30 to 6932.60)
4761.36
(3666.30 to 8852.98)
TNF Alpha Day 3 Number Analyzed 5 participants 25 participants
3791.84
(2108.68 to 4360.80)
3495.45
(2314.73 to 5610.040)
TNF Alpha Day 4 Number Analyzed 5 participants 25 participants
2517.90
(1248.72 to 2950.66)
3411.555
(1894.673 to 6369.735)
TNF Alpha Day 7 Number Analyzed 5 participants 25 participants
694.575
(479.288 to 909.863)
3320.97
(1872.72 to 5481.28)
TNF Alpha Day 10 Number Analyzed 0 participants 25 participants
2361.60
(1741.88 to 3880.690)
MIP-Beta Day 1 Number Analyzed 5 participants 25 participants
4949.89
(4450.56 to 13543.400)
11527.80
(6800.60 to 18611.90)
MIP-Beta Day 2 Number Analyzed 5 participants 25 participants
3066.80
(2566.10 to 10702.90)
8822.96
(5286.89 to 14864.72)
MIP-Beta Day 3 Number Analyzed 5 participants 25 participants
4031.04
(2107.66 to 6968.00)
6594.00
(3215.19 to 8202.60)
MIP-Beta Day 4 Number Analyzed 5 participants 25 participants
2730.50
(2327.64 to 5768.16)
7375.96
(2856.50 to 13588.94)
MIP-Beta Day 7 Number Analyzed 5 participants 25 participants
247.775
(225.088 to 270.463)
5986.40
(3251.41 to 12216.24)
MIP-Beta Day 10 Number Analyzed 0 participants 25 participants
8957.13
(4132.15 to 17056.82)
5.Secondary Outcome
Title Duration of Pleural Drainage as Measured in Postoperative Fontan Patients Treated Empirically With Colchicine
Hide Description Duration is measured in days, from date of Fontan surgery to chest tube drainage discontinuation.
Time Frame Date of chest tube drainage discontinuation, approximately 11 days after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat compared to colchicine per protocol
Arm/Group Title Colchicine Intention to Treat Colchicine Per Protocol
Hide Arm/Group Description:

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

This group were all of those who began the protocol, whether they completed it or not.

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These patients completed the entire protocol.

Overall Number of Participants Analyzed 9 5
Median (Inter-Quartile Range)
Unit of Measure: days
7.5
(5.75 to 9)
6
(4.5 to 7)
6.Secondary Outcome
Title Difference of Duration of Pleural Drainage of Two Groups, in Empiric Treatment With Colchicine Compared to a Cohort of Fontan Patients Not Treated With Colchicine
Hide Description Duration is measured in days, from date of Fontan surgery to chest tube drainage discontinuation
Time Frame Date of chest tube drainage discontinuation, approximately 11 days after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Colchicine Per Protocol Colchinine Intention to Treat Historical Controls
Hide Arm/Group Description:

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These participants completed the protocol.

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These participants were in the trial at least initially, but not all completed the protocol.

Historical Controls were post-operative Fontan patients who underwent their operation at the University of Michigan. They were part of a prospective observational study that was published in 2019 which included the chest tube drainage sample collection similar to that done with the Colchicine cohort in this trial.
Overall Number of Participants Analyzed 5 9 25
Median (Inter-Quartile Range)
Unit of Measure: days
6
(4.5 to 7)
7.5
(5.8 to 9)
10
(7 to 11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Colchicine Per Protocol, Historical Controls
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Colchinine Intention to Treat, Historical Controls
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Hospital Length of Stay as Measured in Postoperative Fontan Patients Treated Empirically With Colchicine
Hide Description Measured in days, from date of Fontan surgery to chest tube drainage discontinuation
Time Frame Hospital discharge at study completion, approximately 2 weeks after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Colchicine Intention to Treat Colchicine Per Protocol
Hide Arm/Group Description:

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These patients were all those assigned to the protocol whether they completed it or not.

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These patients completed the entire protocol.

Overall Number of Participants Analyzed 9 5
Median (Inter-Quartile Range)
Unit of Measure: days
9
(6.5 to 11)
7
(5.5 to 8.5)
8.Secondary Outcome
Title Difference in Hospital Length of Stay
Hide Description Measured in days compared to historical controls
Time Frame Hospital discharge at study completion, approximately 2 weeks after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Colchicine Per Protocol Colchicine Intention to Treat Historical Controls
Hide Arm/Group Description:

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

These patients completed the entire protocol.

All patients entered the intended protocol where Colchicine was empirically given 0.6mg once daily to postoperative Fontan patients starting on postoperative day 2 and ending 1 day after chest tubes were removed or for a maximum of 4 weeks.

All of these participants began the protocol, but not all these participants completed the protocol.

Historical Controls were post-operative Fontan patients who underwent their operation at the University of Michigan. They were part of a prospective observational study that was published in 2019 which included the chest tube drainage sample collection similar to that done with the Colchicine cohort in this trial.
Overall Number of Participants Analyzed 5 9 25
Median (Inter-Quartile Range)
Unit of Measure: days
7
(5.5 to 8.5)
9
(6.5 to 11)
11
(9 to 13)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Colchicine Per Protocol, Historical Controls
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Colchicine Intention to Treat, Historical Controls
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame from initiation of study through 5-14 days after last dose of colchicine (generally 12 -21 days)
Adverse Event Reporting Description As noted earlier under Participant Flow, historical controls were not considered enrolled in this trial. Further, the historical control information comes from an observational study in which Adverse Events were not collected. Thus, historical control data is not presented.
 
Arm/Group Title Colchicine
Hide Arm/Group Description

Colchicine will be given at 0.6 mg once daily for the duration of chest tube output plus 24 hours after chest tube removal with a maximum of 4 weeks duration.

Colchicine: Colchicine is an alkaloid approved in 1961 for the use in Familial Mediterranean Fever in adults and children 4 years of age or older. It has been widely used for decades in other indications, such as Gout, recurrent pericarditis, pericardial effusions and other inflammatory diseases. This drug is commercially available and is approved in children 4 years and older.

All-Cause Mortality
Colchicine
Affected / at Risk (%)
Total   0/9 (0.00%) 
Hide Serious Adverse Events
Colchicine
Affected / at Risk (%)
Total   0/9 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Colchicine
Affected / at Risk (%)
Total   9/9 (100.00%) 
Gastrointestinal disorders   
nausea   5/9 (55.56%) 
diarrhea   1/9 (11.11%) 
vomiting   5/9 (55.56%) 
loose stool   1/9 (11.11%) 
abdominal pain   1/9 (11.11%) 
Hepatobiliary disorders   
hepatic dysfunction   1/9 (11.11%) 
Renal and urinary disorders   
increase in creatinine   1/9 (11.11%) 
Respiratory, thoracic and mediastinal disorders   
pleural effusion   1/9 (11.11%) 
Skin and subcutaneous tissue disorders   
rash   1/9 (11.11%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Stephanie Goldstein
Organization: University of Utah
Phone: 801 587-7572
EMail: stephanie.goldstein@hsc.utah.edu
Layout table for additonal information
Responsible Party: Stephanie Goldstein, University of Michigan
ClinicalTrials.gov Identifier: NCT03575572    
Other Study ID Numbers: HUM00143571
First Submitted: June 18, 2018
First Posted: July 2, 2018
Results First Submitted: February 28, 2022
Results First Posted: May 9, 2022
Last Update Posted: May 9, 2022