Graft FailurePhase 3HOTNCT01430156
Induction of HO-1; a Therapeutic Approach to Reduce Ischaemia Reperfusion Injury (IRI) Following Deceased Donor Renal Transplantation
A Phase 3 study testing Heme arginate (Normosang) and 0.9% sodium chloride in people with Graft Failure and Ischemia-reperfusion Injury, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
This is a blinded, placebo-controlled, randomised controlled trial looking at the effects of Heme arginate (HA) on cadaveric renal transplantation. The investigators know that HA can upregulate HO-1, which has been shown to have a protective effect on animal transplants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Failure, Ischemia-reperfusion Injury
- What is being tested?
- Heme arginate (Normosang) and 0.9% sodium chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2012to Aug 2013
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- all patients receiving a cadaveric single kidney transplant
- patients on a standard immunosuppressive regime
Who cannot join
- patients on different immunosuppressives
- patients receiving 3rd or subsequent kidney transplant
- patients are fully anti-coagulated
- patients unable to take Heme Arginate
- patients unable to give informed consent
- patients on combined anti-platelet agents
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Infirmary of Edinburgh/ University of Edinburgh
Edinburgh, Lothian, EH16 4TJ
About this study
Official title: A Randomised Placebo-Controlled Trial to Investigate the Effect of Pre-treatment With Haem Arginate (Normosang) on Heme-Oxygenase 1 (HO-1) Upregulation in Recipients of Deceased Donor Kidneys
This is a blinded, placebo-controlled, randomised controlled trial looking at the effects of Heme arginate (HA) on cadaveric renal transplantation. The investigators know that HA can upregulate HO-1, which has been shown to have a protective effect on animal transplants.
The investigators will be giving HA/placebo to participants prior to transplant and repeat again on day 2 post-transplant and compare outcomes.
Read the detailed description
Patients will be recruited from the East of Scotland transplant waiting list and consent when they arrive in the hospital. The investigators will randomise them to drug or placebo and give the infusion prior to induction for their transplant.
A blood sample will be taken prior to infusion and a renal biopsy will be taken before the graft is implanted. These will be used as baseline values.
Patients will receive standard care from our unit. The investigators will use the routine blood test results (urea and creatinine) to determine the function of the graft.
The investigators will take blood samples 24 hours after infusion of drug/placebo and use this to determine the primary outcome. Blood tests will be taken daily and a renal biopsy taken on day 5 to fulfil secondary objectives.
- Conditions
- Graft Failure, Ischemia-reperfusion Injury
- Being tested
- Heme arginate (Normosang), 0.9% sodium chloride
- Keywords
- Renal Transplantation, Ischemia-reperfusion injury, Heme-oxygenase 1, Heme arginate
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heme arginate (Normosang)Drug
Also called Heme Arginate, Hemin
3mg/kg as a single IV infusion prior to transplant over 30 mins and same dose repeated on day 2 post-transplantation. Each drug infusion will be followed by 100ml saline IV to flush the line.
0.9% sodium chlorideDrug
Also called Normal saline
Solution for infusion, this will be given prior to transplantation and again on day 2; the same as active drug.
| Study group | Role | What they receive |
|---|---|---|
| Heme arginate (Normosang) | Active comparator | This arm will receive 2 doses of Heme Arginate (trade name Normosang); 1 dose prior to transplant and another on day 2. This is a product derived from human hemin and has been used for over 20 years in clinical practice with few side-effects. Receives: Drug: Heme arginate (Normosang) |
| 0.9% saline | Placebo comparator | The saline will be given as an IV infusion in the same manner as the Heme Arginate (active comparator) infusion. Receives: Drug: 0.9% sodium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Macrophage/monocyte HO-1 protein levels
We will measure the level of HO-1 protein in isolated macrophages/ monocytes in a peripheral blood sample taken at 24 hours after drug infusion
Measured: 24 hours
Secondary outcomes (4)
Macrophage/monocyte HO-1 mRNA levels
We will measure HO-1 mRNA levels in macrophages/monocytes from a peripheral blood sample taken at 24 hours.
Measured: 24 hours
HO-1 protein in kidney transplant
We will measure the level of HO-1 protein in kidney tissue from a biopsy sample taken 5 days after drug infusion. This will be compared to baseline
Measured: 5 days
Effect on transplanted kidney function
We will record how the kidney functions by determining presence or absence of delayed graft function.
Measured: daily for 5 days
Urinary biomarkers as markers of injury
We will collect urine to measure the presence of specific urinary biomarkers and correlate with renal function.
Measured: daily for 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2011 (estimated)
- Study startJan 2012
- Primary completionJun 2013
- Study completionAug 2013
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 Graft FailureStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
- Investigators
- Lorna Marson, MD, Study director, Senior Lecturer, Transplant Surgery, University of EdinburghRachel Thomas, MBChB, Principal investigator, Clinical Research Fellow, University of EdinburghStephen McNally, PhD, Principal investigator, University of EdinburghDavid Kluth, PhD, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01430156
- Sponsor's protocol ID
- HOT-2011
- Other IDs
- 2011-004311-23
- Acronym
- HOT
- Status last verified
- May 2015
- First submitted
- 30 Aug 2011
- Last updated
- 27 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Thomas RA, Czopek A, Bellamy CO, McNally SJ, Kluth DC, Marson LP. Hemin Preconditioning Upregulates Heme Oxygenase-1 in Deceased Donor Renal Transplant Recipients: A Randomized, Controlled, Phase IIB Trial. Transplantation. 2016 Jan;100(1):176-83. doi: 10.1097/TP.0000000000000770.
PubMed 26680374
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Placebo-Controlled Trial to Investigate the Effect of Pre-treatment With Haem Arginate (Normosang) on Heme-Oxygenase 1 (HO-1) Upregulation in Recipients of Deceased Donor Kidneys
- ClinicalTrials.gov ID
- NCT01430156
- Acronym / sponsor ID
- HOT / HOT-2011
- Conditions
- Graft Failure, Ischemia-reperfusion Injury
- Keywords
- Renal Transplantation, Ischemia-reperfusion injury, Heme-oxygenase 1, Heme arginate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- Jan 2012
- Primary completion
- Jun 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 7 Sep 2011 (estimated)
- 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 is a blinded, placebo-controlled, randomised controlled trial looking at the effects of Heme arginate (HA) on cadaveric renal transplantation. The investigators know that HA can upregulate HO-1, which has been shown to have a protective effect on animal transplants.
The investigators will be giving HA/placebo to participants prior to transplant and repeat again on day 2 post-transplant and compare outcomes.
Detailed description
Patients will be recruited from the East of Scotland transplant waiting list and consent when they arrive in the hospital. The investigators will randomise them to drug or placebo and give the infusion prior to induction for their transplant.
A blood sample will be taken prior to infusion and a renal biopsy will be taken before the graft is implanted. These will be used as baseline values.
Patients will receive standard care from our unit. The investigators will use the routine blood test results (urea and creatinine) to determine the function of the graft.
The investigators will take blood samples 24 hours after infusion of drug/placebo and use this to determine the primary outcome. Blood tests will be taken daily and a renal biopsy taken on day 5 to fulfil secondary objectives.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Heme arginate (Normosang) | Active comparator | Drug: Heme arginate (Normosang)This arm will receive 2 doses of Heme Arginate (trade name Normosang); 1 dose prior to transplant and another on day 2. This is a product derived from human hemin and has been used for over 20 years in clinical practice with few side-effects. |
| 0.9% saline | Placebo comparator | Drug: 0.9% sodium chlorideThe saline will be given as an IV infusion in the same manner as the Heme Arginate (active comparator) infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- all patients receiving a cadaveric single kidney transplant
- patients on a standard immunosuppressive regime
Key exclusion criteria (6 listed)
- patients on different immunosuppressives
- patients receiving 3rd or subsequent kidney transplant
- patients are fully anti-coagulated
- patients unable to take Heme Arginate
- patients unable to give informed consent
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 |
|---|---|---|
| Heme arginate (Normosang)Also: Heme Arginate, Hemin3mg/kg as a single IV infusion prior to transplant over 30 mins and same dose repeated on day 2 post-transplantation. Each drug infusion will be followed by 100ml saline IV to flush the line. | Drug | Heme arginate (Normosang) |
| 0.9% sodium chlorideAlso: Normal salineSolution for infusion, this will be given prior to transplantation and again on day 2; the same as active drug. | Drug | 0.9% saline |
Primary outcome
Macrophage/monocyte HO-1 protein levels
Time frame: 24 hours
We will measure the level of HO-1 protein in isolated macrophages/ monocytes in a peripheral blood sample taken at 24 hours after drug infusion
4 secondary outcomes
Macrophage/monocyte HO-1 mRNA levels
Time frame: 24 hours
HO-1 protein in kidney transplant
Time frame: 5 days
Effect on transplanted kidney function
Time frame: daily for 5 days
Urinary biomarkers as markers of injury
Time frame: daily for 5 days
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 27 May 2015.
- Derived from this study: PubMed 26680374Thomas RA, Czopek A, Bellamy CO, McNally SJ, Kluth DC, Marson LP. Hemin Preconditioning Upregulates Heme Oxygenase-1 in Deceased Donor Renal Transplant Recipients: A Randomized, Controlled, Phase IIB Trial. Transplantation. 2016 Jan;100(1):176-83. doi: 10.1097/TP.0000000000000770.
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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.
Lorna Marson, MD study director
Senior Lecturer, Transplant Surgery, University of Edinburgh
Rachel Thomas, MBChB principal investigator
Clinical Research Fellow, University of Edinburgh
Stephen McNally, PhD principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Heme arginate (Normosang) and 0.9% sodium chloride in people with Graft Failure and Ischemia-reperfusion Injury, run by University of Edinburgh at 1 site in United Kingdom.
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 2 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 27 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Macrophage/monocyte HO-1 protein levels (time frame: 24 hours). 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 NCT01430156, 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 27 May 2015.