METHOD OF TREATING PATIENTS WITH HEPATORENAL SYNDROME TYPE 1

• US 20190328831A1
• Filed: 05/14/2019
• Published: 10/31/2019
• Est. Priority Date: 10/24/2014
• Status: Abandoned Application

• Current Assignee: Mallinckrodt Pharmaceuticals Ireland Limited (Mallinckrodt plc)
• Original Assignee: Mallinckrodt Hospital Products IP Ltd. (Mallinckrodt plc)
• Inventors: Jamil, Khurram, Pappas, Stephen Chris, Potenziano, Jim
• Application Number:
  US16/411,944
• Publication Number:
  US 20190328831A1
• Time in Patent Office: Days
• CPC Class Codes: A61B 5/0205 Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 38/38 Albumins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61M 27/002 Implant devices for drainage of body fluids from one part of the body to another intraocular A61F9/00781; middle ear A61F11/202
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: A61P 5/38 of the suprarenal hormones
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: G01N 15/10 Investigating individual particles
• CPC Class Codes: G01N 2015/016 White blood cells
• CPC Class Codes: G01N 2015/1024 Counting particles by non-optical means
• CPC Class Codes: G01N 33/4925 measuring blood gas content, e.g. O2, CO2 , HCO3

Abstract

The principles and embodiments of the present disclosure relate to methods for using terlipressin to treat a patient having impaired renal function associated with liver disease. A patient identified as suffering from HRS-1 is tested to determine if the patient meets at least two out of three criteria, wherein the three criteria include a WBC<4 or >12 cells/4; HR>90 bpm; and any one of HCO3<21 mmol/L or PaCO2<32 mmHg or >20 breaths per minute. If the patient meets at least two of the criteria, he or she is administered terlipressin in an amount effective to produce a reduction in serum creatinine of at least 1.0 mg/dL.

Claims

1. A method for treating HRS-1, the method comprising:

diagnosing a plurality of patients as having HRS-1;

determining that a first and a second patient of the plurality do not have overt sepsis, septic shock, or uncontrolled infection;

testing the first and second patients to determine whether each meets each of the following three criteria (i)-(iii);

(i) a white blood cell count either less than 4,000 cells/mm³ or greater than 12,000 cells/mm³,

(ii) a heart rate of greater than 90 beats per minute, and

(iii) either (a) a partial pressure of carbon dioxide in the blood (PaCO₂) of <

32 mmHg or (b) a blood bicarbonate (HCO₃) level of <

23 mmol/L or (c) tachypnea with more than 20 breaths per minute;

determining that the first patient meets at least two of the three criteria;

determining that, because the first patient meets at least two of the three criteria, the first patient'"'"'s renal function is more likely to improve upon treatment with terlipressin than if the first patient exhibited only one or none of the three criteria;

initiating administration of terlipressin to the first patient within two days of the determination that the first patient meets at least two of the three criteria, wherein the terlipressin is administered as an IV in an amount effective to reduce the first patient'"'"'s serum creatinine level by at least 1.0 mg/dL;

determining that the second patient meets only one or none of the three criteria;

determining that, because the second patient does not meet at least two of the three criteria, the second patient'"'"'s renal function is less likely to respond to treatment with terlipressin than if the second patient exhibited at least two of the three criteria; and

excluding the second patient from treatment with terlipressin.

2. The method of claim 1, wherein a treatment other than terlipressin is administered to the second patient.

3. The method of claim 2, wherein the second patient is treated with one or more of nor-epinephrine, vasopressin, or a combination of midodrine and octreotide.

4. The method of claim 2, wherein the second patient is given a transjugular intrahepatic portosystemic shunt.

5. The method of claim 2, wherein the second patient is treated with kidney dialysis.

6. The method of claim 1, wherein criterion (iii) is a HCO₃ level<

23 mmol/L.

7. The method of claim 1, wherein criterion (iii) is a HCO₃ level<

21 mmol/L.

8. The method of claim 1, wherein the first patient is administered terlipressin as an IV every 4 to 6 hours for 4 days.

9. A method of identifying a subset of HRS-1 patients with an increased likelihood of responding to treatment with terlipressin compared to other HRS-1 patients, the method comprising:

identifying a plurality of patients who have type 1 hepatorenal syndrome and who do not have overt sepsis, septic shock, or uncontrolled infection;

for each patient of the plurality, measuring at least two of the following three variables (a)-(c);

variable (a);

white blood cell count;

variable (b);

number of heart beats per minute;

variable (c);

either blood HCO₃ level or PaCO₂ level or breaths per minute;

within the plurality of patients, identifying a subset comprising one or more patients, all of whom meet at least two of the following three criteria (i)-(iii);

(i) a white blood cell count either less than 4,000 cells/mm³ or greater than 12,000 cells/mm³,

(ii) a heart rate of greater than 90 beats per minute, and

(iii) either HCO₃<

23 mmol/L or PaCO₂<

32 mmHg or >

20 breaths per minute, wherein other patients of the plurality meet only one or none of the three criteria, so are not in the subset; and

determining that the one or more patients in the subset have an increased likelihood of responding to treatment with terlipressin compared to the other patients of the plurality who are not in the subset.

10. The method of claim 9, comprising treating at least one patient of the subset with terlipressin;

measuring the at least one patient'"'"'s serum creatinine level after treatment has begun; and

observing that the serum creatinine level in the blood of the at least one patient decreased upon treatment with terlipressin.

11. The method of claim 10, comprising excluding from terlipressin treatment the patients of the plurality who meet only one or none of the three criteria, so are not in the subset.

12. The method of claim 9, wherein criterion (iii) is a HCO₃ level<

23 mmol/L.

13. The method of claim 9, wherein criterion (iii) is a HCO₃ level<

21 mmol/L.

14. A method of distributing a pharmaceutical product, the method comprising:

supplying terlipressin to a medical provider responsible for treating a patient suffering from type 1 hepatorenal syndrome;

providing a recommendation to the medical provider to treat a patient who (a) is suffering from type 1 hepatorenal syndrome, (b) does not have overt sepsis, septic shock, or uncontrolled infection, and (c) meets two or more of the following three criteria (i)-(iii);

(i) a white blood cell count either less than 4,000 cells/mm³ or greater than 12,000 cells/mm³,

(ii) a heart rate of greater than 90 beats per minute, and

(iii) either HCO₃<

23 mmol/L or PaCO₂<

32 mmHg or >

20 breaths per minute, with terlipressin in an amount effective to reduce the patient'"'"'s serum creatinine level.

15. The method of claim 14, wherein criterion (iii) is a HCO₃ level<

23 mmol/L.

16. The method of claim 14, wherein criterion (iii) is a HCO₃ level<

21 mmol/L.