Iron-deficiencyNCT03707249
Iron Status and Cardiopulmonary Physiology
A study testing Ferric Carboxymaltose Injectable Product and Normal Saline 0.9% Infusion Solution Bag in people with Iron-deficiency and Ventricular Function, run by Royal Centre for Defence Medicine.
Trial summary
This study involved human volunteers undertaking a high-altitude expedition. It assessed changes in physiological parameters of relevance to high-altitude cardiopulmonary physiology. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Iron-deficiency, Ventricular Function, Pulmonary Vascular Resistance Abnormality
- What is being tested?
- Ferric Carboxymaltose Injectable Product and Normal Saline 0.9% Infusion Solution Bag
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- 19 Jan 2016to 7 Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy non-pregnant adults
- Age 18-55 years
- Serving in the UK Armed Forces
- Selected for a military mountaineering team intending to climb to very high altitude
Who cannot join
- Diabetes
- Any cardiovascular or respiratory illness
- Regular medication which would interfere with any outcome measures in the study
- Pregnancy
- Any condition which precludes the administration of Ferinject:
- hypersensitivity to the active substance, to Ferinject® or any of its excipients (ii) known serious hypersensitivity to other parenteral iron products (iii) microcytic anaemia not attributable to iron deficiency (e.g. sickle cell anaemia) (iv) evidence of iron overload or disturbances in the utilisation of iron.
About this study
Official title: Effects of Iron Status, Manipulated Using Intravenous Iron, on Cardiopulmonary Physiology During Ascent to Very High Altitude
This study involved human volunteers undertaking a high-altitude expedition. It assessed changes in physiological parameters of relevance to high-altitude cardiopulmonary physiology. Participants included a subgroup of those taking part in an existing adventurous training expedition and were randomised in a 1:1 fashion to receive either intravenous iron or normal saline several weeks prior to departure. During the expedition, participants were investigated by means of transthoracic echocardiography, peripheral oxygen saturation measurement and heart rate monitoring and through the drawing of venous blood samples. Bloods were later analysed for markers of iron status.
Read the detailed description
Aim
The aim of the study was to investigate the effects of iron status on human cardiopulmonary physiology during ascent to very high altitude. Differences in iron status were brought about using intravenous iron, and outcomes were assessed using echocardiography and self-reported functional performance scores.
Objectives
Principal objective: To compare echocardiographic parameters in individuals of differing iron status during the expedition.
Secondary objectives: To compare physiological variables (oxygen saturation, pulse) and self-reported functional measures, in individuals of differing iron status during the expedition.
Hypotheses
The primary hypothesis was that iron status, manipulated using intravenous iron, would influence the echocardiographic indices of cardiopulmonary physiological function over the course of the ascent.
A secondary hypothesis was that iron status would influence cardiopulmonary responses in terms of pulse and oxygen saturation, and additionally the perceived exertion involved in ascent to very high altitude.
Design of the Study
The study randomised 18 individuals to iron or normal saline in a 1:1 ratio giving two groups of 9 people. The randomised infusion (control or iron) was undertaken at a pre-expedition meeting approximately 2 weeks prior to the flight to Nepal. The profile of ascent to high altitude will followed internationally accepted acclimatisation guidelines.
Preliminary Testing
To exclude elevated iron stores prior to enrollment, participants underwent an initial blood test. At the pre-exercise mounting station, prior to the flight to Nepal, baseline echocardiography was performed, and blood samples were collected immediately prior to randomisation and infusion. All blood samples in the study were analysed for full blood count, ferritin, iron, transferrin and C-reactive protein (CRP).
Expedition-based tests
Waking peripheral oxygen saturation (%) of haemoglobin (SpO2) and pulse were recorded daily. Venous blood samples were taken for later analysis of variables relevant to iron homeostasis including full blood count, erythropoietin, soluble transferrin receptor and hepcidin. These samples were taken in Kathmandu on the morning following arrival, at the intermediate staging camp (~3,200m) and then at the Dhaulagiri base camp on arrival and after descents from 6,000m and 7,000m.
Measures of both left and right heart function were performed and included: pulmonary artery systolic pressure, pulmonary acceleration time, pulmonary regurgitation end diastolic velocity and tricuspid annular plane systolic excursion (distance of systolic excursion of the right ventricular annular plane towards the apex - TAPSE). Echo parameters were acquired and processed by an appropriately experienced researcher. Measures were taken during exercise on arrival at each test altitude and at rest the following morning. Measurements taken from climbers returning from either 6,000 m or 7,000 m were taken as soon as possible after their return to base camp.
Subjective ratings scales include those for breathlessness (Borg 1-10) and perceived exertion (Borg 6-20).
Blood sample storage and analysis
Once drawn, venous blood was placed on ice. Following centrifugation (3,500 rpm for 10 minutes at 4OC), aliquots of plasma were stored in cryogenic vials at -20°C. Samples drawn at high altitude were transported on dry ice or in liquid nitrogen 'dry-shippers' (safe liquid nitrogen containers that cannot leak nitrogen as liquid) back to the UK (United Kingdom). Subsequent analysis was performed at the University of Oxford.
Statistical analysis
Data were analysed using statistical tests with International Business Machines (IBM) 'statistical package for social sciences' (SPSS) version 22 software.
- Conditions
- Iron-deficiency, Ventricular Function, Pulmonary Vascular Resistance Abnormality, Altitude Hypoxia
- Being tested
- Ferric Carboxymaltose Injectable Product, Normal Saline 0.9% Infusion Solution Bag
- Medical subject headings
- Anemia, Iron-Deficiency, Altitude Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferric Carboxymaltose Injectable ProductDrug
Also called Ferinject
iv iron infusion: 15 mg / kg up to a maximum 1g dose of Ferinject diluted in normal saline (0.9%) up to a total volume of 250 ml
Normal Saline 0.9% Infusion Solution BagDrug
250 ml of normal (0.9%) saline given by intravenous infusion over 20 minutes. This constitutes the control for the iron infusion.
| Study group | Role | What they receive |
|---|---|---|
| Iron | Experimental | Received a blinded single 15 mg/kg dose of iv ferric carboxymaltose (Ferinject) up to a maximum off 1g total dose 2 weeks prior to ascent to very high-altitude. Receives: Drug: Ferric Carboxymaltose Injectable Product |
| Saline control | Sham comparator | Received a blinded single dose of iv normal saline 2 weeks prior to ascent to very high-altitude. Receives: Drug: Normal Saline 0.9% Infusion Solution Bag |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in right ventricular systolic pressure (RVSP) with altitude
Non-invasive measurement of Right ventricular systolic pressure (mmHg) estimated from the velocity of tricuspid regurgitation (TR) (m/s) measured during transthoracic echocardiographic (TTE) continuous wave (CW) Doppler assessment of the tricuspid valve regurgitant jet (RVSP = TR velocity^2 * 4)
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in time from pulmonary valve opening to peak pulmonary flow velocity with altitude
The time from pulmonary valve opening to peak velocity flow is inversely correlated with pulmonary artery pressure. This time is measured on a pulsed wave (PW) Doppler trace in the parasternal short axis view at the pulmonary valve level. The measurement is a time and the units are ms. Categories are: normal (>130 ms), borderline elevated (100-130 ms), elevated (80-100 ms) and severely elevated (<80 ms).
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in left ventricular stroke volume (LV SV) with altitude
The stroke volume of the left ventricle is calculated from 2-D parasternal echocardiographic measurement of the left ventricular outflow tract diameter (LVOT) and pulsed wave (PW) Doppler measurement of the flow through the LVOT during systole. PW of the LVOT allows measurement of the velocity.time integral of the LVOT flow (VTI). This value, when multiplied by the cross sectional area of the LVOT, allows an extimate of stroke volume. SV = (Pi*(radius of LVOT^2))*VTI of LVOT
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in left ventricular index of myocardial performance (LIMP) with altitude
This is a non-invasive measurement of left ventricular function made by transthoracic echocardiography (TTE). Tissue Doppler imaging (TDI) is used to measure the behaviour of the left ventricle throughout the cardiac cycle (both systole and diastole). This allows the time (ms) of isovolumic contraction time (ICT), isovolumic relaxation time (IVRT) and ejection time (ET). The LIMP (also known as Tei index) = IVCT+IVRT/ET. It is a global measure of systolic and diastolic function of the heart.
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in right ventricular index of myocardial performance (RIMP) with altitude
This is a non-invasive measurement of right ventricular function made by transthoracic echocardiography (TTE). Tissue Doppler imaging (TDI) is used to measure the behaviour of the left ventricle throughout the cardiac cycle (both systole and diastole). This allows the time (ms) of isovolumic contraction time (ICT), isovolumic relaxation time (IVRT) and ejection time (ET). The RIMP = IVCT+IVRT/ET. It is a global measure of systolic and diastolic function of the heart.
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in tissue Doppler velocity of the Right Ventricle (RV) and Left Ventricle (LV); units: cm/s, with altitude
Tissue Doppler imaging (TDI) is performed on the ventricular myocardium 1cm apical to the atrioventricular valve annulus (either the tricuspid valve annulus, for the RV assessment, or the LV septum and LV lateral wall adjacent to the mitral valve for the LV assessment). The parameters are peak systolic velocity (s', cm/s), peak velocity during early diastole (e', cm/s) and peak velocity during atrial systole (a', cm/s).
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in tricuspid annulus planar systolic excursion (TAPSE) with altitude
This is a Doppler M-mode measurement of the full range of movement of the tricuspid annulus at the right ventricular (RV) free wall throughout the cardiac cycle. It is measured by placing an M-mode cursor through the connection of the tricuspid annulus to the RV free wall and measuring the basal-apical excursion of the annulus at this point, from end diastole until the most apical point that it reaches in systole. It is a measure of systolic RV function. Its units are cm.
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in right and left ventricular strain with altitude
Non-invasive tissue Doppler measurements are acquired on apical 4-chamber, apical 2-chamber and apical 3-chamber images throughout 3 cardiac cycles to allow later analysis to determine the longitudinal strain of the right and left ventricle
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Secondary outcomes (7)
Change in peripheral oxygen saturation with altitude
Peripheral oxygen saturation measured using a non-invasive portable, fingertip pulse oximeter
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in heart rate with altitude
Heart rate measured by 3 lead ECG monitor connected to a portable transthoracic echocardiography machine
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in blood ferritin level (ug/L) with altitude
Venous blood samples analysed for ferritin
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in haemoglobin level (g/dL) with altitude
Venous blood samples analysed for haemoglobin
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in transferrin saturation (%) with altitude
Venous blood samples analysed for transferrin and iron to allow the calculation of the transferrin saturation, listed as a percentage
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in soluble transferrin receptor level (nmol/L) with altitude
Venous blood samples analysed for soluble transferrin receptor
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in hepcidin level (ng/mL) with altitude
Venous blood samples analysed for hepcidin
Measured: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start19 Jan 2016
- Primary completion1 May 2016
- Study completion7 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Iron-deficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2 groups were randomised to receive a dose of intravenous iron or iv saline control to manipulate body iron stores. They were subsequently investigated non-invasively and with venous blood sampling during an ascent to very high altitude.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Centre for Defence Medicine
- Sponsor type
- Other government
- Collaborators
- University of Oxford
- Responsible party
- Principal investigator, Lieutenant Colonel David Holdsworth, Royal Centre for Defence Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03707249
- Sponsor's protocol ID
- 663/MODREC/15
- Status last verified
- Oct 2018
- First submitted
- 1 Oct 2018
- Last updated
- 18 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Holdsworth DA, Frise MC, Bakker-Dyos J, Boos C, Dorrington KL, Woods D, Mellor A, Robbins PA. Iron bioavailability and cardiopulmonary function during ascent to very high altitude. Eur Respir J. 2020 Sep 17;56(3):1902285. doi: 10.1183/13993003.02285-2019. Print 2020 Sep.
PubMed 32430412
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Iron Status, Manipulated Using Intravenous Iron, on Cardiopulmonary Physiology During Ascent to Very High Altitude
- ClinicalTrials.gov ID
- NCT03707249
- Acronym / sponsor ID
- 663/MODREC/15
- Conditions
- Iron-deficiency, Ventricular Function, Pulmonary Vascular Resistance Abnormality, Altitude Hypoxia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Royal Centre for Defence MedicineOther government
- Collaborators
- University of Oxford
- Study start
- 19 Jan 2016 (actual)
- Primary completion
- 1 May 2016 (actual)
- Study completion
- 7 Dec 2017 (actual)
- First posted
- 16 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study involved human volunteers undertaking a high-altitude expedition. It assessed changes in physiological parameters of relevance to high-altitude cardiopulmonary physiology. Participants included a subgroup of those taking part in an existing adventurous training expedition and were randomised in a 1:1 fashion to receive either intravenous iron or normal saline several weeks prior to departure. During the expedition, participants were investigated by means of transthoracic echocardiography, peripheral oxygen saturation measurement and heart rate monitoring and through the drawing of venous blood samples. Bloods were later analysed for markers of iron status.
Detailed description
Aim
The aim of the study was to investigate the effects of iron status on human cardiopulmonary physiology during ascent to very high altitude. Differences in iron status were brought about using intravenous iron, and outcomes were assessed using echocardiography and self-reported functional performance scores.
Objectives
Principal objective: To compare echocardiographic parameters in individuals of differing iron status during the expedition.
Secondary objectives: To compare physiological variables (oxygen saturation, pulse) and self-reported functional measures, in individuals of differing iron status during the expedition.
Hypotheses
The primary hypothesis was that iron status, manipulated using intravenous iron, would influence the echocardiographic indices of cardiopulmonary physiological function over the course of the ascent.
A secondary hypothesis was that iron status would influence cardiopulmonary responses in terms of pulse and oxygen saturation, and additionally the perceived exertion involved in ascent to very high altitude.
Design of the Study
The study randomised 18 individuals to iron or normal saline in a 1:1 ratio giving two groups of 9 people. The randomised infusion (control or iron) was undertaken at a pre-expedition meeting approximately 2 weeks prior to the flight to Nepal. The profile of ascent to high altitude will followed internationally accepted acclimatisation guidelines.
Preliminary Testing
To exclude elevated iron stores prior to enrollment, participants underwent an initial blood test. At the pre-exercise mounting station, prior to the flight to Nepal, baseline echocardiography was performed, and blood samples were collected immediately prior to randomisation and infusion. All blood samples in the study were analysed for full blood count, ferritin, iron, transferrin and C-reactive protein (CRP).
Expedition-based tests
Waking peripheral oxygen saturation (%) of haemoglobin (SpO2) and pulse were recorded daily. Venous blood samples were taken for later analysis of variables relevant to iron homeostasis including full blood count, erythropoietin, soluble transferrin receptor and hepcidin. These samples were taken in Kathmandu on the morning following arrival, at the intermediate staging camp (~3,200m) and then at the Dhaulagiri base camp on arrival and after descents from 6,000m and 7,000m.
Measures of both left and right heart function were performed and included: pulmonary artery systolic pressure, pulmonary acceleration time, pulmonary regurgitation end diastolic velocity and tricuspid annular plane systolic excursion (distance of systolic excursion of the right ventricular annular plane towards the apex - TAPSE). Echo parameters were acquired and processed by an appropriately experienced researcher. Measures were taken during exercise on arrival at each test altitude and at rest the following morning. Measurements taken from climbers returning from either 6,000 m or 7,000 m were taken as soon as possible after their return to base camp.
Subjective ratings scales include those for breathlessness (Borg 1-10) and perceived exertion (Borg 6-20).
Blood sample storage and analysis
Once drawn, venous blood was placed on ice. Following centrifugation (3,500 rpm for 10 minutes at 4OC), aliquots of plasma were stored in cryogenic vials at -20°C. Samples drawn at high altitude were transported on dry ice or in liquid nitrogen 'dry-shippers' (safe liquid nitrogen containers that cannot leak nitrogen as liquid) back to the UK (United Kingdom). Subsequent analysis was performed at the University of Oxford.
Statistical analysis
Data were analysed using statistical tests with International Business Machines (IBM) 'statistical package for social sciences' (SPSS) version 22 software.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 2 groups were randomised to receive a dose of intravenous iron or iv saline control to manipulate body iron stores. They were subsequently investigated non-invasively and with venous blood sampling during an ascent to very high altitude.
| Arm | Type | Receives |
|---|---|---|
| Iron | Experimental | Drug: Ferric Carboxymaltose Injectable ProductReceived a blinded single 15 mg/kg dose of iv ferric carboxymaltose (Ferinject) up to a maximum off 1g total dose 2 weeks prior to ascent to very high-altitude. |
| Saline control | Sham comparator | Drug: Normal Saline 0.9% Infusion Solution BagReceived a blinded single dose of iv normal saline 2 weeks prior to ascent to very high-altitude. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy non-pregnant adults
- Age 18-55 years
- Serving in the UK Armed Forces
- Selected for a military mountaineering team intending to climb to very high altitude
Key exclusion criteria (6 listed)
- Diabetes
- Any cardiovascular or respiratory illness
- Regular medication which would interfere with any outcome measures in the study
- Pregnancy
- Any condition which precludes the administration of Ferinject:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ferric Carboxymaltose Injectable ProductAlso: Ferinjectiv iron infusion: 15 mg / kg up to a maximum 1g dose of Ferinject diluted in normal saline (0.9%) up to a total volume of 250 ml | Drug | Iron |
| Normal Saline 0.9% Infusion Solution Bag250 ml of normal (0.9%) saline given by intravenous infusion over 20 minutes. This constitutes the control for the iron infusion. | Drug | Saline control |
Primary outcome
Change in right ventricular systolic pressure (RVSP) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Non-invasive measurement of Right ventricular systolic pressure (mmHg) estimated from the velocity of tricuspid regurgitation (TR) (m/s) measured during transthoracic echocardiographic (TTE) continuous wave (CW) Doppler assessment of the tricuspid valve regurgitant jet (RVSP = TR velocity^2 * 4)
Change in time from pulmonary valve opening to peak pulmonary flow velocity with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
The time from pulmonary valve opening to peak velocity flow is inversely correlated with pulmonary artery pressure. This time is measured on a pulsed wave (PW) Doppler trace in the parasternal short axis view at the pulmonary valve level. The measurement is a time and the units are ms. Categories are: normal (>130 ms), borderline elevated (100-130 ms), elevated (80-100 ms) and severely elevated (<80 ms).
Change in left ventricular stroke volume (LV SV) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
The stroke volume of the left ventricle is calculated from 2-D parasternal echocardiographic measurement of the left ventricular outflow tract diameter (LVOT) and pulsed wave (PW) Doppler measurement of the flow through the LVOT during systole. PW of the LVOT allows measurement of the velocity.time integral of the LVOT flow (VTI). This value, when multiplied by the cross sectional area of the LVOT, allows an extimate of stroke volume. SV = (Pi*(radius of LVOT^2))*VTI of LVOT
Change in left ventricular index of myocardial performance (LIMP) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
This is a non-invasive measurement of left ventricular function made by transthoracic echocardiography (TTE). Tissue Doppler imaging (TDI) is used to measure the behaviour of the left ventricle throughout the cardiac cycle (both systole and diastole). This allows the time (ms) of isovolumic contraction time (ICT), isovolumic relaxation time (IVRT) and ejection time (ET). The LIMP (also known as Tei index) = IVCT+IVRT/ET. It is a global measure of systolic and diastolic function of the heart.
Change in right ventricular index of myocardial performance (RIMP) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
This is a non-invasive measurement of right ventricular function made by transthoracic echocardiography (TTE). Tissue Doppler imaging (TDI) is used to measure the behaviour of the left ventricle throughout the cardiac cycle (both systole and diastole). This allows the time (ms) of isovolumic contraction time (ICT), isovolumic relaxation time (IVRT) and ejection time (ET). The RIMP = IVCT+IVRT/ET. It is a global measure of systolic and diastolic function of the heart.
Change in tissue Doppler velocity of the Right Ventricle (RV) and Left Ventricle (LV); units: cm/s, with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Tissue Doppler imaging (TDI) is performed on the ventricular myocardium 1cm apical to the atrioventricular valve annulus (either the tricuspid valve annulus, for the RV assessment, or the LV septum and LV lateral wall adjacent to the mitral valve for the LV assessment). The parameters are peak systolic velocity (s', cm/s), peak velocity during early diastole (e', cm/s) and peak velocity during atrial systole (a', cm/s).
Change in tricuspid annulus planar systolic excursion (TAPSE) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
This is a Doppler M-mode measurement of the full range of movement of the tricuspid annulus at the right ventricular (RV) free wall throughout the cardiac cycle. It is measured by placing an M-mode cursor through the connection of the tricuspid annulus to the RV free wall and measuring the basal-apical excursion of the annulus at this point, from end diastole until the most apical point that it reaches in systole. It is a measure of systolic RV function. Its units are cm.
Change in right and left ventricular strain with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Non-invasive tissue Doppler measurements are acquired on apical 4-chamber, apical 2-chamber and apical 3-chamber images throughout 3 cardiac cycles to allow later analysis to determine the longitudinal strain of the right and left ventricle
7 secondary outcomes
Change in peripheral oxygen saturation with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in heart rate with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in blood ferritin level (ug/L) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in haemoglobin level (g/dL) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in transferrin saturation (%) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in soluble transferrin receptor level (nmol/L) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Change in hepcidin level (ng/mL) with altitude
Time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2018.
- Derived from this study: PubMed 32430412Holdsworth DA, Frise MC, Bakker-Dyos J, Boos C, Dorrington KL, Woods D, Mellor A, Robbins PA. Iron bioavailability and cardiopulmonary function during ascent to very high altitude. Eur Respir J. 2020 Sep 17;56(3):1902285. doi: 10.1183/13993003.02285-2019. Print 2020 Sep.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Ferric Carboxymaltose Injectable Product and Normal Saline 0.9% Infusion Solution Bag in people with Iron-deficiency and Ventricular Function, run by Royal Centre for Defence Medicine.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in right ventricular systolic pressure (RVSP) with altitude (time frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03707249, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2018; AzTrials last refreshed its copy on 26 Oct 2026.