Claims for Patent: 10,335,452

Summary for Patent: 10,335,452

Title:	Method of treating patients with hepatorenal syndrome type 1
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/μL; HR>90 bpm; and any one of HCO<21 mmol/L or PaCO<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.
Inventor(s):	Jamil Khurram, Pappas Stephen Chris, Potenziano Jim
Assignee:	Mallinckrodt Hospital Products IP Limited
Application Number:	US14920392
Patent Claims:	1. A method of treating type 1 hepatorenal syndrome (HRS-1) , the method comprising:identifying a plurality of patients as having HRS-1; [{'sup': 3', '3, '(i) a white blood cell count (WBC) less than 4,000 cells/mmor greater than 12,000 cells/mm,'}, '(ii) a heart rate of greater than 90 beats per minute (BPM), and', {'sub': 2', '3, '(iii) either a partial pressure of carbon dioxide in the blood (PaCO)<32 mmHg or a blood bicarbonate (HCO) level<23 mmol/L;'}], 'determining that a first patient of the plurality exhibits at least two of the following three criteria for Systemic Inflammatory Response Syndrome (SIRS)determining that the first patient does not have overt sepsis, septic shock, or uncontrolled infection;determining that, because the first patient exhibits at least two of the three criteria and does not have overt sepsis, septic shock, or uncontrolled infection, the HRS-1 of the first patient is likely to respond to treatment with terlipressin;administering to the first patient an amount of terlipressin effective to treat HRS-1 in the first patient;determining that a second patient of the plurality exhibits only one or none of the three criteria or has overt sepsis, septic shock, or uncontrolled infection;determining that, because the second patient does not exhibit at least two of the three criteria or has overt sepsis, septic shock, or uncontrolled infection, the HRS-1 of the second patient is unlikely to respond to treatment with terlipressin;excluding the second patient from treatment with terlipressin determining that a third patient of the plurality has overt sepsis, septic shock, or uncontrolled infection; andexcluding the third 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 1 , wherein criterion (iii) is a HCO3 level<23 mmol/L.4. The method of claim 1 , wherein criterion (iii) is a HCO3 level<21 mmol/L.5. The method of claim 1 , wherein the amount of terlipressin administered to the first patient is in the range of 2.0 mg to 12.0 mg per day for 1 to 28 days.6. The method of claim 5 , wherein the amount of terlipressin administered to the first patient is in the range of about 0.5 mg to about 2.0 mg every 4 to 6 hours.7. The method of claim 1 , comprising determining if the first patient has a reduction in serum creatinine level during the initial 1 to 4 days of terlipressin administration.8. The method of claim 7 , comprising discontinuing administration of terlipressin to the first patient if the first patient does not show a reduction in serum creatinine level during the initial 1 to 4 days of terlipressin administration.9. The method of claim 7 , comprising continuing administration of terlipressin to the first patient for an additional 3 to 12 days if the first patient shows a reduction in serum creatinine level during the initial 1 to 4 days of terlipressin administration.10. The method of claim 1 , wherein administration of terlipressin to the first patient produces a decrease in serum creatinine level to ≤1.5 mg/dl.11. The method of claim 1 , comprising treating the first patient with up to a maximum of 100 g per day of albumin for each day of the time period that the first patient is administered terlipressin.12. The method of claim 1 , wherein administering terlipressin to the first patient provides reversal of one or more complicating factors.13. The method of claim 12 , wherein one or more of the complicating factors is splanchnic vasodilation.14. The method of claim 12 , wherein reversal of one or more complicating factors reduces mortality from an associated complication within a 90 day window starting with administering the terlipressin.15. A method of increasing the effectiveness of terlipressin for the treatment of impaired renal function associated with liver disease claim 12 , comprising:identifying a plurality of patients with end-stage liver disease and impaired renal function; [{'sup': 3', '3, '(i) a white blood cell count either less than 4,000 cells/mmor greater than 12,000 cells/mm,'}, '(ii) a heart rate of greater than 90 beats per minute, and', {'sub': 2', '3, '(iii) either (a) a partial pressure of carbon dioxide in the blood (PaCO) of <32 mmHg or (b) a blood bicarbonate HCOlevel of <23 mmol/L or (c) tachypnea with more than 20 breaths per minute;'}], 'testing the plurality of patients to determine whether each meets each of the following three criteria (i)-(iii)determining that a first patient of the plurality meets at least two of the three criteria;determining that the first patient does not have overt sepsis, septic shock, or uncontrolled infection;determining that, because the first patient meets at least two of the three criteria and does not have overt sepsis, septic shock, or uncontrolled infection, 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;administering to the first patient an amount of terlipressin effective to improve the first patient's renal function;determining that a second patient of the plurality meets only one or none of the three criteria or has overt sepsis, septic shock, or uncontrolled infection;determining that, because the second patient does not meet at least two of the three criteria or has overt sepsis, septic shock, or uncontrolled infection, 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; andexcluding the second patient from treatment with terlipressin.16. The method of claim 15 , wherein claim 15 , during treatment with terlipressin claim 15 , the first patient is tested to determine if the first patient's renal function is improved compared to prior to treatment with terlipressin.17. The method of claim 15 , wherein a treatment other than terlipressin is administered to the second patient.18. The method of claim 15 , wherein criterion (iii) is a HCO3 level<23 mmol/L.19. The method of claim 15 , wherein criterion (iii) is a HCO3 level<21 mmol/L.20. The method of claim 15 , comprising determining that a third patient of the plurality has overt sepsis claim 15 , septic shock claim 15 , or uncontrolled infection claim 15 , and excluding the third patient from treatment with terlipressin because of the presence of overt sepsis claim 15 , septic shock claim 15 , or uncontrolled infection.21. The method of claim 15 , comprising determining that the plurality of patients have cirrhosis of the liver with a Child-Pugh score of B or C.22. The method of claim 15 , wherein the dosage of terlipressin administered to the first patient over a 4 hour to 6 hour period is in the range of about 0.5 mg to about 2.0 mg.23. The method of claim 15 , wherein the terlipressin is administered to the first patient as a continuous IV drip.24. The method of claim 15 , wherein the dosage of terlipressin administered to the first patient does not exceed 4.0 mg over each 24 hour period of administration.25. The method of claim 15 , comprising determining a baseline serum creatinine level for the first patient within 2 days prior to starting the administration of terlipressin to the first patient and testing the first patient at least once within four days after starting the administration of terlipressin to determine if the first patient's serum creatinine level has decreased compared to the baseline level.26. The method of claim 25 , wherein the administration of terlipressin to the first patient is continued if testing the first patient's serum creatinine level after starting the administration of terlipressin shows that the first patient's serum creatinine level has decreased compared to the baseline level claim 25 , and the administration is discontinued if the first patient's serum creatinine level has not decreased compared to the baseline level.27. The method of claim 26 , wherein the first patient's serum creatinine level is shown to have decreased compared to the baseline level claim 26 , and then administration of terlipressin to the first patient is continued for an additional 3 days to 8 days.28. The method of claim 15 , wherein claim 15 , following treatment with terlipressin claim 15 , the first patient's serum creatinine level is tested and found to be ≤1.5 mg/dl.