Clinical Trial Results:
Copper Chelation in Hypertrophic Cardiomyopathy: Openlabel pilot study of Trientine in patients with hypertrophic cardiomyopathy
Summary


EudraCT number 
201400157713 
Trial protocol 
GB 
Global end of trial date 
02 Sep 2016

Results information


Results version number 
v1(current) 
This version publication date 
04 Jun 2020

First version publication date 
04 Jun 2020

Other versions 
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 
CCHCM01


Additional study identifiers


ISRCTN number 
  
US NCT number 
  
WHO universal trial number (UTN) 
U111111556428  
Other trial identifiers 
REC reference: 14/NW/1015  
Sponsors


Sponsor organisation name 
Manchester University NHS Foundation Trust


Sponsor organisation address 
29 Grafton Street, Manchester, United Kingdom, M13 9WU


Public contact 
Dr Lynne Webster, Head of the Research Office , Manchester University NHS Foundation Trust, +44 161 276 4125, research.sponsor@mft.nhs.uk


Scientific contact 
Anna Reid, Manchester University NHS Foundation Trust, +44 7743647285, Anna.Reid@MFT.NHS.UK


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 
02 Sep 2016


Is this the analysis of the primary completion data? 
No


Global end of trial reached? 
Yes


Global end of trial date 
02 Sep 2016


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
i. Does Trientine lead to an improvement in highenergy phosphate metabolism (myocardial energetics, i.e. energy processing) in patients with HCM?


Protection of trial subjects 
Patients may develop adverse effects whilst taking Trientine.These risks will be fully explained to patients before they decide to participate in the trial. After patients have completed this clinical study, Trientine will be discontinued. Although Trientine is a licensed medication, it may not be possible to prescribe it “offlabel”, even if some of the patients have benefited from it. This will be made clear to patients before they enrol in the trial. MRI scanning is a standard clinical imaging modality in every day clinical use and risks to study participants from MRI scanning are very small, provided they do not have any contraindications to MRI scanning (patients with contraindications to MRI scanning will be excluded). Echocardiography is a standard clinical imaging modality in every day clinical use.


Background therapy 
N/A  
Evidence for comparator 
There is no comparator in this trial.  
Actual start date of recruitment 
10 Oct 2014


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
No


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
United Kingdom: 22


Worldwide total number of subjects 
22


EEA total number of subjects 
22


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
18


From 65 to 84 years 
4


85 years and over 
0



Recruitment


Recruitment details 
Recruitment to the trial opened on 10/10/2014 following R&D approval and sponsor green light. A total of 23 participants were recruited to the trial but four withdrew prior to completion.  
Preassignment


Screening details 
Inclusion criteria:  Male or female > 18 years of age  Females will be nonpregnant and nonlactating with no intention of pregnancy during study treatment*  Confirmed diagnosis of HCM in line with 2011 ACCF / AHA consensus document  Positive genotype  LV ejection fraction ≥ 50%  
Period 1


Period 1 title 
Trientine (overall period)


Is this the baseline period? 
Yes  
Allocation method 
Not applicable


Blinding used 
Not blinded  
Blinding implementation details 
N/A  there is no placebo or active comparator so there is no blinding in this trial.


Arms


Arm title

Trientine tablets  
Arm description 
Patients will be supplied with Trientine tablets. The starting dose prescribed will be 600mg per day (taken as 300mg twice daily) for the first week, followed by 1200mg/day (taken as 600mg twice daily) thereafter under the direction of a medical doctor. The study doctor will contact each patient after 1 week to ensure they feel well enough to continue, and if they do, to remind them to increase their dose.  
Arm type 
Experimental  
Investigational medicinal product name 
Trientine dihydrochloride


Investigational medicinal product code 
SUB04953MIG


Other name 
PL 41626/0001


Pharmaceutical forms 
Tablet


Routes of administration 
Oral use


Dosage and administration details 
Trientine dihydrochloride is a divalent copper selective chelator. It forms a stable complex with divalent copper. This complex is readily excreted by the kidney, increasing copper excretion. It also reduces intestinal absorption. Patients will be supplied with Trientine tablets. The starting dose prescribed will be 600mg per day (taken as 300mg twice daily) for the first week, followed by 1200mg/day (taken as 600mg twice daily) thereafter under the direction of a medical doctor. The study doctor will contact each patient after 1 week to ensure they feel well enough to continue, and if they do, to remind them to increase their dose.





Baseline characteristics reporting groups


Reporting group title 
Trientine


Reporting group description 
  



End points reporting groups


Reporting group title 
Trientine tablets


Reporting group description 
Patients will be supplied with Trientine tablets. The starting dose prescribed will be 600mg per day (taken as 300mg twice daily) for the first week, followed by 1200mg/day (taken as 600mg twice daily) thereafter under the direction of a medical doctor. The study doctor will contact each patient after 1 week to ensure they feel well enough to continue, and if they do, to remind them to increase their dose. 


End point title 
LVM ^{[1]}  
End point description 

End point type 
Primary


End point timeframe 
Visit 6


Notes [1]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a pilot trial with no comparator group. Results are given as descriptive statistics only with comparisons to baseline (p=0.06). 



No statistical analyses for this end point 


End point title 
Native septal T1 ^{[2]}  
End point description 

End point type 
Primary


End point timeframe 
Visit 6


Notes [2]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a pilot trial with no comparator group. Results are given as descriptive statistics only with comparisons to baseline (p=0.06). 



No statistical analyses for this end point 


End point title 
ECV Fraction ^{[3]}  
End point description 

End point type 
Primary


End point timeframe 
Visit 6


Notes [3]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a pilot trial with no comparator group. Results are given as descriptive statistics only with comparisons to baseline (p=0.06). 



No statistical analyses for this end point 


End point title 
PCr/ATP Ratio ^{[4]}  
End point description 

End point type 
Primary


End point timeframe 
Visit 6


Notes [4]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a pilot trial with no comparator group. Results are given as descriptive statistics only with comparisons to baseline (p=0.46). 



No statistical analyses for this end point 


End point title 
Haemoglobin  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Urea  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Creatinine  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
eGFR  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Alk Phos  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
ALT  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Magnesium  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Serum Copper  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Serum Caeruloplasmin  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Serum Zinc  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Systolic BP  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Diastolic BP  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
BSA  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
E velocity  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
A velocity  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
E/A ratio  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Mean S* Velocity  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Mean E* Velocity  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Mean A* Velocity  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Mean E/E*  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Mitral Decel. Time  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Exercise time  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Anaerobic Threshold  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
VO2 Max  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
PR interval  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
QRS duration  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
QTc  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Heart rate  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LVEDV  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LVESV  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
SV  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LVEDVi  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LVESVi  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
SVi  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LVMi  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
EF  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Total Myocardial Volume  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
ECM Volume  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Cellular Volume  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
GLS  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LAESV  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LAEDV  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Preatrial contraction vol  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LAESVi  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LAEDVi  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Preatrial contraction vol i  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Total EP  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Passive EF  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Booster EF  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
LA Expansion Index  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Total strain  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Peak systolic strain rate  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Passive Strain  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Peak early negative strain rate  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Active Strain  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


End point title 
Peak late negative strain rate  
End point description 

End point type 
Secondary


End point timeframe 
Visit 6




No statistical analyses for this end point 


Adverse events information


Timeframe for reporting adverse events 
Adverse events assessed by the study investigators were recorded and followed up until resolution.


Assessment type 
Nonsystematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
1


Reporting groups


Reporting group title 
Trientine tablets


Reporting group description 
Patients will be supplied with Trientine tablets. The starting dose prescribed will be 600mg per day (taken as 300mg twice daily) for the first week, followed by 1200mg/day (taken as 600mg twice daily) thereafter under the direction of a medical doctor. The study doctor will contact each patient after 1 week to ensure they feel well enough to continue, and if they do, to remind them to increase their dose.  


Frequency threshold for reporting nonserious adverse events: 0%  



Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

26 Feb 2015 
Substantial amendment 1:
 Addition of St Mary's Hospital, CMFT as a PIC site.
 Addition of instructions for use of the cool bag system.
The amendment received REC favourable opinion 23/03/2015. 

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. 