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Heme Arginate in Transplantation Study (HOT2)

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ClinicalTrials.gov Identifier: NCT03646344
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : April 17, 2019
Sponsor:
Collaborator:
Kidney Cancer UK
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:

Organ shortage for transplant has necessitated use of kidneys from older donors, increasing the chance that the kidney will not work immediately or for as long as expected. The investigators gave the drug heme arginate (HA) to 20 kidney transplant patients in the first 24 hours after transplant, and showed that it may reduce kidney injury and is safe. The investigators plan to conduct a large study recruiting 600 patients to determine whether HA treatment increases the number of kidney transplants that work immediately. If successful, HA may be introduced into clinical practice at the end of this study.

Patients will be invited to take part in the study once listed for a kidney transplant. Further discussions will be had with them when admitted for transplant, and they will be offered the opportunity to participate. Consent will not be taken until the patient is admitted for transplantation. Following consent, participants will be randomised to receive either 2 doses of the study drug, HA, or a salt water solution, one at the time of transplant, and one approximately 24 hours later. Otherwise, treatment will be the same as any other patient undergoing a kidney transplant. Information about recovery from surgery, and specifically about kidney function, will be collected, but will not require additional blood tests. The study period ends after the first 7 days post-transplant, although longer term data will be collected from routine follow up appointments. Participants will be asked to complete a simple quality of life questionnaire 3 times: just before transplant, at approximately one week and three months after transplant.


Condition or disease Intervention/treatment Phase
Renal Transplant Rejection Renal Transplant Failure Drug: Heme Arginate 25 MG/ML Drug: 0.9% Sodium-chloride Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multi-centre, parallel group 1:1 randomised placebo controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: There will be an unblinded member of the research team (the individual administering the intervention) but otherwise the participant, the other members of the research team, the clinical team and blinded assessors will be blinded to the intervention.
Primary Purpose: Treatment
Official Title: Heme Arginate in Transplantation Study - a Multi-centre Blinded Parallel-group Randomised Trial of Heme Arginate Versus Placebo to Reduce Delayed Graft Function in Kidney Transplant Recipients
Actual Study Start Date : March 12, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active Group
Will receive Heme Arginate (IMP) at a dose of 3mg/kg over 30mins. Participants will receive infusions of the IMP at 2 time-points, the first prior to surgery (transplantation), and the second 20-28 hours later. At each infusion, the IMP will be followed by a 100ml infusion of 0.9% Sodium Chloride over 15mins.
Drug: Heme Arginate 25 MG/ML
IMP - to be administered at a dose of 3mg/kg to a maximum dose of 250mg over 30 mins. Participants will receive intervention twice during the trial, one on Day 0 (day of transplantation) and then again on D1 (20-28 hours after dose 1).

Placebo Comparator: Placebo Group
Will receive a 100ml infusion of 0.9% Sodium Chloride (placebo) over 30mins. Participants will receive infusions at 2 time-points, the first prior to surgery, and the second 20-28 hours later. At each infusion, the placebo will be followed by a further 100ml infusion of 0.9% Sodium Chloride over 15mins.
Drug: 0.9% Sodium-chloride
Placebo - 100ml of 0.9% Sodium Chloride will be given over 30 mins. Participants will receive intervention twice during the trial, one on Day 0 (day of transplantation) and then again on D1 (20-28 hours after dose 1).




Primary Outcome Measures :
  1. Delayed Graft Function [ Time Frame: 1 week post transplant ]
    The incidence of delayed graft function, defined as failure of a spontaneous fall in creatinine of >10% for each 3 consecutive day period in the first week following transplantation, with comparison between the two randomised groups.


Secondary Outcome Measures :
  1. Requirement for dialysis [ Time Frame: 1 week post transplant ]
    The number of participants requiring dialysis within the first week post-transplant

  2. Time to functioning graft [ Time Frame: 1 week ]
    The number of days to functioning graft, defined as the spontaneous fall in creatinine of greater than, or equal to 10% over a period of 3 consecutive days in the first 7 days post transplant

  3. Length of hospital stay [ Time Frame: 3 months ]
    The number of days spent in hospital, along with level of care (ward/HDU/ITU), for the index admission (transplantation admission)

  4. Creatinine levels [ Time Frame: 3 months ]
    Serum creatinine levels at 1 and 3 months post-transplant across both randomised groups

  5. Acute rejection [ Time Frame: 3 months ]
    The number of participants with biopsy-proven acute rejection within the first 3 months post-transplant

  6. SF36 Quality of Life [ Time Frame: Up to 3 months post transplant ]
    A comparison of differences between groups in patient reported quality of life using the SF36

  7. Cost per QALY gained [ Time Frame: Up to 3 months post transplant ]
    Using data derived from the SF36 to weight survival for quality of life, Quality Adjusted Life Year (QALY) will be assessed


Other Outcome Measures:
  1. 1 Year graft survival [ Time Frame: 1 year ]
    Graft survival rates at 1 year post transplant will be obtained from routinely collected data and differences between treatment groups assessed.

  2. 1 year recipient survival [ Time Frame: 1 year ]
    Recipient survival rates at 1 year post transplant will be obtained from routinely collected data and differences between treatment groups assessed.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients undergoing a kidney only transplant, or a dual kidney transplant, from a deceased donor
  • At least 18 years of age, no upper limit
  • Receiving standard immunosuppression for the individual centre
  • (where applicable) Meets co-enrolment criteria outlined in section 4.4 of the protocol

Exclusion Criteria:

  • Kidney transplant patients as part of a multi-organ transplant e.g. with pancreas or liver
  • Known hypersensitivity to heme arginate
  • Unable to give informed consent
  • Patients with porphyria, irrespective of whether they have received heme arginate or not, will be excluded
  • Previous randomisation into this study (or HOT study)
  • Women who are pregnant or lactating
  • Kidneys that have undergone Ex-vivo Normothermic Perfusion (EVNP)
  • Patients with known liver disease, epilepsy, brain injury or disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03646344


Contacts
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Contact: Jean Antonelli 01316519920 Jean.Antonelli@ed.ac.uk

Locations
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United Kingdom
NHS Lothian - Royal Infirmary of Edinburgh Recruiting
Edinburgh, Lothian, United Kingdom, EH16 4SA
Contact: Jean Antonelli    01316519920    Jean.Antonelli@ed.ac.uk   
Principal Investigator: Andrew Sutherland         
Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh Active, not recruiting
Edinburgh, United Kingdom, EH16 4UX
Sponsors and Collaborators
University of Edinburgh
Kidney Cancer UK
Investigators
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Principal Investigator: Lorna Marson University of Edinburgh

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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT03646344     History of Changes
Other Study ID Numbers: AC17065
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Following publication of the primary paper, a de-identified individual participant data set will be submitted to a data archive for sharing purposes. Access to this data set will be under a controlled access model in line with ECTU policies at that time.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Edinburgh:
Deceased donor renal transplantation
Heme Arginate
Delayed graft function

Additional relevant MeSH terms:
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Delayed Graft Function
Pathologic Processes