Trial Outcomes & Findings for Testosterone and Myocardial Perfusion in Coronary Heart Disease (CHD) (NCT NCT00239590)

Last Updated: 2019-09-25

Results Overview

Myocardial perfusion (blood flow in the heart muscle) in subendocardial myocardial segments (one of the inner layers of heart muscle), supplied by coronary arteries without significant obstruction. This was measured using Cardiovascular Magnetic Resonance (CMR) imaging and a dual-bolus gadnolinium infusion protocol. Myocardial perfusion index = the ratio between myocardial perfusion measurements following adenosine-induced stress and rest measurements.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Testosterone versus placebo (8 week treatment period)

Results posted on

2019-09-25

Participant Flow

Outpatients at a tertiary referral NHS hospital in London, UK. Eligible patients were invited to participate by post. Interested participants returned an eligibility questionnaire. Those fulfilling the inclusion/exclusion criteria were invited to attend for a screening/consent appointment.

Blood was taken at a screening visit. Those not fulfulling the inclusion/exclusion criterial were excluded.

Participant milestones

Participant milestones
Measure	Testosterone (First, Then Placebo) oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks. At the end of 8 weeks, patients were evaluated, then crossed-over to placebo for 8 weeks. No wash-out period. Testosterone undecanoate: Licensed for androgen deficiency	Placebo (First, Then Testosterone) identical to active medication, taken in an identical way to the active arm for 8 weeks. At the end of the 8 week placebo treatment phase evaluation visit, patients crossed-over to the testosterone treatment arm for 8 weeks. No wash-out period.
Randomized STARTED	14	14
Randomized COMPLETED	14	12
Randomized NOT COMPLETED	0	2
Started Intervention After Randomization STARTED	14	12
Started Intervention After Randomization COMPLETED	14	12
Started Intervention After Randomization NOT COMPLETED	0	0
Completed Study Protocol STARTED	14	12
Completed Study Protocol COMPLETED	13	10
Completed Study Protocol NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Testosterone (First, Then Placebo) oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks. At the end of 8 weeks, patients were evaluated, then crossed-over to placebo for 8 weeks. No wash-out period. Testosterone undecanoate: Licensed for androgen deficiency	Placebo (First, Then Testosterone) identical to active medication, taken in an identical way to the active arm for 8 weeks. At the end of the 8 week placebo treatment phase evaluation visit, patients crossed-over to the testosterone treatment arm for 8 weeks. No wash-out period.
Randomized Lost to Follow-up	0	1
Randomized Withdrawal by Subject	0	1
Completed Study Protocol Adverse Event	1	1
Completed Study Protocol Withdrawal by Subject	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=28 Participants All participants randomized to study medication (n=28), whether randomized to testosterone or placebo first.
Age, Categorical <=18 years	0 Participants n=28 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=28 Participants
Age, Categorical >=65 years	8 Participants n=28 Participants
Sex: Female, Male Female	0 Participants n=28 Participants
Sex: Female, Male Male	28 Participants n=28 Participants
Region of Enrollment United Kingdom	28 participants n=28 Participants

PRIMARY outcome

Timeframe: Testosterone versus placebo (8 week treatment period)

Population: 22 patients had assessable CMR data for both evaluation visits.

Outcome measures

Outcome measures
Measure	Testosterone n=22 Participants Pooled first and second treatment phase data. oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks. Testosterone undecanoate: Licensed for androgen deficiency	Placebo n=22 Participants pooled first and second treatment phase data
Myocardial Perfusion	1.83 myocardial perfusion index Standard Deviation 0.9	1.52 myocardial perfusion index Standard Deviation 0.65

SECONDARY outcome

Timeframe: Testosterone versus placebo (8 week treatment period)

Population: A total of 17 patients had endothelial function assessments - the same patients took both interventions in a randomized cross-over design.

The endothelium is a single layer of cells that line all blood vessels and regulates arterial function. Coronary artery disease causes dysfunction of the endothelium but some substances/drugs help to reverse this dysfunction. In this study, endothelial function was measured by radial applanation tonometry which measures the blood pressure waveform during each cardiac cycle (heart beat). Radial artery pulse recordings were acquired, with an averaged waveform generated from 20 sequential waveforms. Augmentation index (AIx) is derived from this averaged waveform, and is the ratio of the pulse pressure at the second systolic arterial pressure waveform peak to that of the first systolic peak. The change in AIx before and after salbutamol (400mcg) is a measure of endothelial function.

Outcome measures

Outcome measures
Measure	Testosterone n=17 Participants Pooled first and second treatment phase data. oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks. Testosterone undecanoate: Licensed for androgen deficiency	Placebo n=17 Participants pooled first and second treatment phase data
Endothelial Function	76.5 Augmentation index Standard Deviation 9.5	79.4 Augmentation index Standard Deviation 7.8

Adverse Events

Testosterone

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Testosterone n=28 participants at risk oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks Testosterone undecanoate: Licensed for androgen deficiency Active and placebo given in a cross-over design	Placebo n=28 participants at risk identical to active medication, taken in an identical way to the active arm
Nervous system disorders Hospitalization	3.6% 1/28 • Number of events 1 • Event data were collected from time of participant inclusion in the study until the end of the final study visit (end of the second treatment phase and assessment visit) - a total of approximately 20 weeks. There was no formal long-term follow-up.	0.00% 0/28 • Event data were collected from time of participant inclusion in the study until the end of the final study visit (end of the second treatment phase and assessment visit) - a total of approximately 20 weeks. There was no formal long-term follow-up.

Other adverse events

Other adverse events
Measure	Testosterone n=28 participants at risk oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks Testosterone undecanoate: Licensed for androgen deficiency Active and placebo given in a cross-over design	Placebo n=28 participants at risk identical to active medication, taken in an identical way to the active arm
Nervous system disorders Low mood	0.00% 0/28 • Event data were collected from time of participant inclusion in the study until the end of the final study visit (end of the second treatment phase and assessment visit) - a total of approximately 20 weeks. There was no formal long-term follow-up.	3.6% 1/28 • Number of events 1 • Event data were collected from time of participant inclusion in the study until the end of the final study visit (end of the second treatment phase and assessment visit) - a total of approximately 20 weeks. There was no formal long-term follow-up.

Additional Information

Dr Carolyn Webb

Imperial College London

Phone: 03301288860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place