Peritoneal Ultrafiltration in Cardio Renal Syndrome to Prevent Heart Failure Exacerbation (PURE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Iperboreal Pharma S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

6 Mar 2024 → ongoing

Decision date (initial)

2024-05-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512658-41-00

EudraCT number

2019-004670-25

ClinicalTrials.gov

NCT03994874

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Evaluate if the treatment with Peritoneal Ultrafiltration with PolyCore has an impact on the composite endpoint of patient’s mortality or worsening of patient’s condition

Secondary objectives 10

1. Evaluate the the improvement of patients’ conditions
2. Evaluate the changes in the Quality of Life
3. Evaluate the changes in the use of hospital resources
4. Evaluate the changes in NYHA class
5. Evaluate the changes in kidney function
6. Evaluate urine output and urine sodium preservation
7. Evaluate the changes in the sympathetic nerve tone
8. Evaluate the need of loop diuretic
9. Evaluate hospitalization requirements
10. Evaluate PolyCore safety

Conditions and MedDRA coding

Congestive Heart Failure

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Adult patients
2. Signed informed consent form for participation in this study
3. Left ventricular ejection fraction ≤60%
4. NYHA Classification of III-IV
5. Persistency of right ventricular failure due to after load mismatch
6. Cava vein enlargement (between 1,5 and 2,5 cm, with respiratory collapse <50% or absent due to intravascular fluid overload)
7. Decreased kidney function with mGFR between 15 and 60 ml/min/1.73m2
8. At least one episode of pulmonary or systemic congestion requiring high-dose intravenous diuretics in the 6 months before the study enrolment
9. Appropriate PUF technique candidate

Exclusion criteria 23

1. Recipients of heart transplantation within one year prior to the screening
2. Presence of a mechanical circulatory support device
3. Hypertrophic obstructive cardiomyopathy
4. Uncontrolled hypertension with systolic blood pressure ≥ 160 mmHg
5. Severe valvular stenosis
6. Acute coronary syndrome ≤ 6 months before screening
7. Active myocarditis
8. Cardiosurgical or Endoradiological heart procedures ≤ 6 month before screening
9. CRT implantation or upgrading of PM or ICD to CRT ≤ 6 months before screening
10. End-stage renal disease (GFR < 15ml/min/1.73m2)
11. Any major organ transplant (liver, lung, kidney)
12. Lung embolism ≤ 6 months before screening
13. Fibrotic lung disease
14. Liver cirrhosis (Child B or C)
15. Absolute contraindication to peritoneal catheter implantation
16. Logistical and or organizational contra-indication to treatment
17. Active malignancy
18. Female patients who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical study and for three months later
19. Female patients of childbearing age who do not use adequate contraception
20. Unwilling or unable to give informed consent
21. Enrolment in another clinical trial involving medical or device-based interventions during a) the 30 days before the screening or b) 5-times the half-life of the used investigational product
22. Ipersensibility to Icodextrin, L-Carnitine, D-xilitol and other PolyCore components
23. Evidence of any condition that, according to the investigators’ judgment, could expose the subject to undue risk and/or prevent the subject from participating in the study procedures and/or potentially affecting the study quality data

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite end point of 1) patient mortality; 2) hospitalization for cardiovascular causes, including the need for i.v. diuretics and/or hemofiltration; 3) The need of increasing of ≥30% the initial daily dose of loop diuretic; 4) Worsening renal function defined as eGRF ˂10 ml/min/1,73 m2

Secondary endpoints 13

1. 6 min Walking distance (V1, V5, V8, V9)
2. Quality of life by Kansas City Cardiomyopathy Questionnaire (V1, V5, V8, V9)
3. Decrease in NT pro-BNT level of >=25% or BNP of >=40% (V1, V5, V8, V9)
4. Change in NYHA class (V1, V5, V8, V9, Long term FU)
5. Hospitalization for intra-venous therapy with loop diuretic
6. Requiring other methods of treatment [i.e. PUF or hemodialysis]
7. Hospitalization for all causes
8. Worsening of renal function defined as % of change of GFR (V1, V3, V4, V5, V6, V7, V8, V9, Long term)
9. Change in the cumulative daily dosage of loop diuretic
10. Use of hospital resources for cardiovascular causes
11. The number of patients requiring hospitalization for intra-venous therapy with loop diuretic
12. The number of patients increasing of ≥30% an equivalent of the daily dose of oral furosemide
13. Safety (adverse events, vital signs, physical examination, ECG, laboratory parameters)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Iperboreal Pharma S.r.l.

Sponsor organisation

Iperboreal Pharma S.r.l.

Address

Via L' Aquila 9, Abruzzo Abruzzo

City

Pescara

Postcode

65121

Country

Italy

Scientific contact point

Organisation

Iperboreal Pharma S.r.l.

Contact name

Arduino Arduini

Public contact point

Organisation

Iperboreal Pharma S.r.l.

Contact name

Arduino Arduini

Third parties 4

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications