Clinical trial NCT03861637: Impact of Full Correction of PTA in Renal Transplant Recipients
Official title: Impact of Full Correction of Post-transplant Anemia on the Cardiovascular System and Quality of Life in Renal Transplant Recipients Receiving Erythropoietin Stimulating Agents: a Prospective Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anemia
Lead sponsor: Hamid Al-Essa Organ Transplant Center
Sponsor class: OTHER_GOV
First posted: 2019-03-04
Enrollment: 280
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: comparison of partially corrected vs. fully corrected PTA in renal transplant recipients
Primary purpose: TREATMENT

Brief summary: Background:

Post-transplant anemia (PTA) might be associated cardiovascular morbidity and even increased mortality. Objectives:

We aimed to assess the impact of full correction of chronic PTA on cardiovascular system and quality of life in renal transplant recipients with stable graft function using erythropoietin stimulating agents.

Patient and methods: We enrolled 247 kidney recipients with stable graft function to be assessed for anemia. Eligible patients were randomized to achieve target hemoglobin between 11 to 12 g/dl (group 1, n=183), or 13 to 15 g/dl (in group 2, n=64) using ESA. Monthly clinical and laboratory evaluation of kidney graft function was carried out. Moreover, quality of life (QOL) and echocardiography were assessed at the start and at 12 months.

Detailed description: Two hundred and eighty anemic renal transplant recipients with stable graft function- who are followed up in Hamed Al-Essa organ transplant centre - will be assessed for the possible causes of their anemia. Anemia will be defined as Revised European Best Practice guidelines for anemia in renal tx, a Hb level of \<11 g/dl should trigger treatment with ESA.

Drugs:

After patients' assessment for possible causes of anemia, each patient will be managed according to the specific cause of anemia i.e. iron, folic, and vitamin b12 deficiencies will be corrected. If anemia will be improved, we will consider such group of patients as corrected group, but if we failed to find specific cause of anemia we will consider them for ESA. Iron supplementation is permitted in order to maintain serum ferritin in the range 100-800 ng/ml or transferring saturation (TSAT) in the range 20-50%. Medications known to affect Hb concentration-e.g. angiotensin converting enzyme inhibitors (ACEI) \& angiotensin receptor blockers (ARBS) - will be maintained at a stable dose if already prescribed at the start of the study.

Patients who fulfilled the following criteria will be included in the study:

Adult renal transplant patients (≥18 years). Informed consent. Stable maintenance subcutaneous darbepoetin alfa therapy with constant dose interval during the last 2 months.

Haemoglobin (Hb) ≥10mg/dL (Hct 32%). Transferrin saturation (TSAT) ≥20% (during the screening phase) Serum ferritin ≥100 ng/mL

We will exclude patients with the following criteria:

Acute or chronic bleeding, or erythrocyte transfusion, within the preceding 8 weeks.

Change in Hb level ≥ 2 g/dL during screening phase. Hemolytic anemia. Recent infection or rejection Diastolic blood pressure \>100mmHg or discontinuation of ESA due to hypertension in the 6 months prior to study.

Vitamin B12 or folic acid deficiency. Uncontrolled or secondary hyperparathyroidism. Acute or chronic systemic inflammatory disease and/or C-reactive protein (CRP) \>30 mg/L.

Hemodialysis due to the failure of a kidney transplant. Malignancy. Eligible patients will be randomized to either target hemoglobin between 11 to 12 gram/dl (group 1), or target hemoglobin between 13 to 15 gram/dl (group 2). The target HB will be achieved using either darbepoetin α once weekly or once every 2 weeks or equivalent dosage of monthly CERA and the dosage will be adjusted during the titration and evaluation phase according to table 1.

The maintenance dosage of each agent will be modified according to the response (hemoglobin changes). In case of any emergencies, the patient will be managed in Hamed Al-Issa organ transplant Centre 24 hours per day. Mobile of the 1st on-call doctor is ( ); Tel of OTC, ward 1(24826490 \&24840300 ext. 4100)".

Randomization:

Patients will be classified according to the maintenance dose of ESA, then they will be sub-grouped into males and females. All patients in each subgroup will be arranged alphabetical using Excel program, and a number will be given to each patient. Patients with odd numbers will serve as group1 while those with even numbers will serve as group 2. Patients' files will be marked with sticker according to the corresponding group to facilitate collection of data.

Methods:

Each patient will be evaluated:

Clinically by history taking and thorough medical examination every month in the outpatient clinic.

By Laboratory investigations which will include:

CBC\*, HB electrophoresis, Iron-Ferritin- Transferrin saturation, PT(INR) B12, folic acid levels PTH, CR protein, ESR

* Serum cr., Cr cl, LFT, ca/ph, FBS
* Urinary protein (gm / 24h )
* Drug levels Virology profile (CMV, EBV, Parvovirus ) The radiological investigation using abdominal US, echocardiography and carotid Doppler ultrasound.

Quality of life will be assessed in each patient using 25 and 36 questionnaires at the start of enrollment and by the end of 12 months of achieving the target hemoglobin.

NB.1- \* indicates that these test will be every month, while other tests will be only at the initial assessment.

2-Blood samples will be sent to the corresponding laboratory without storage and results will be collected according to the laboratory schedule.

3-As the drugs utilized in such study is available for all patients (Kuwaiti and non-Kuwaiti), we will proceed smoothly. However, some of the laboratory tests will need patients own financial support (especially the non-Kuwaiti).

Data analysis:

Descriptive parameters (mean, standard deviation, median, range, and the number of observations) will be presented for continuous observations.

Frequencies (absolute and percentage) are to be shown for qualitative variables (e.g., sex, ethnicity, Hb values within target ranges and occurrence of adverse events).

The safety population will compromise all patients who received at least one dose of study medication. All patients in the safety population who provided at least one Hb value during C.E.R.A. therapy will be included in the intention-to-treat (ITT) population

Eligibility criteria: Inclusion Criteria:

* Patients who fulfilled the following criteria were included in the study:
* Adult renal transplant patients (≥21years),
* Informed consent,
* Stable maintenance subcutaneous ESA therapy with constant dose interval during the last 2 months,
* Haemoglobin (Hb) ≥10mg/dL (Hct 32%),
* Transferrin saturation (TSAT) ≥20% (during the screening phase),
* and serum ferritin ≥100 ng/mL

Exclusion Criteria:

We excluded patients with the following criteria:

* Acute or chronic bleeding, or erythrocyte transfusion, within the preceding 8 weeks. change in Hb level ≥ 2 g/dL during screening phase,
* Hemolytic anemia,
* Recent infection or rejection,
* Diastolic blood pressure \>100mmHg or discontinuation of ESA due to hypertension in the 6 months prior to study,
* Vitamin B12 or folic acid deficiency,
* Uncontrolled or secondary hyperparathyroidism,
* Acute or chronic systemic inflammatory disease and/or C-reactive protein (CRP) \>30 mg/L,
* Hemodialysis due to failure of a kidney transplant,
* and malignancy

Primary outcomes:
measure: 1 year mortality
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: