Method for guidance of fluid therapy based on proadrenomedullin

Patent metadata

Field	Value
Publication number	US-12517138-B2
Application number	US-201816646639-A
Country	US
Kind code	B2
Filing date	Sep 13, 2018
Priority date	Sep 13, 2017
Publication date	Jan 6, 2026
Grant date	Jan 6, 2026

Abstract

The invention relates to a method of therapy guidance, stratification and/or monitoring of fluid therapy based on proadrenomedullin (proADM) levels. The invention therefore relates to a method for therapy guidance, stratification and/or monitoring of a fluid therapy, comprising providing a sample of said patient, determining a level of pro adrenomedullin (proADM) or fragment(s) thereof in said sample, wherein said level of proADM or fragment(s) thereof indicates the prescription of fluid therapy to be administered to the patient. The invention further relates to methods for guiding fluid therapy volume and to methods of treating disease using fluid therapy based on the proADM stratification of patients based on the methods described herein.

First claim

The invention claimed is:

1 . A method for adjusting or not adjusting a fluid therapy being administered to a patient, wherein the method comprises:
obtaining a sample from said patient, determining a level of pro adrenomedullin (proADM) or fragment(s) thereof in said sample, and reducing the volume, frequency and/or rate of fluid administered to the patient when the level of proADM or fragment(s) thereof in the sample is determined to be at an intermediate or high severity level, or not adjusting the volume, frequency and/or rate of fluid administered to the patient when the level of proADM or fragment(s) thereof in the sample is determined to be at low severity level, wherein a low severity level of proADM or one or more fragments thereof is below 2.75 nmol/l, wherein an intermediate severity level of proADM or one or more fragments thereof is from 2.75 nmol/l to 10.9 nmol/l, and wherein a high severity level of proADM or one or more fragments thereof is above 10.9 nmol/l.

2 . The method according to claim 1 , wherein
a patient with a low severity level of proADM or fragment(s) thereof determined in the sample is administered at most 2.78 ml/kg of body weight of fluid within approximately 24 hours after the sample was obtained from the patient, a patient with an intermediate severity level of proADM or fragment(s) thereof determined in the sample is administered at most 4.94 ml/kg of body weight of fluid within approximately 24 hours after the sample was obtained from the patient, a patient with a high severity level of proADM or fragment(s) thereof determined in the sample is administered at most 9.95 ml/kg of body weight of fluid within approximately 24 hours after the sample was obtained from the patient, and wherein a low severity level of proADM or fragment(s) thereof is below 2.75 nmol/l, wherein an intermediate severity level of proADM or fragment(s) thereof is from 2.75 nmol/l to 10.9 nmol/l, and wherein a high severity level of proADM or fragment(s) thereof is above 10.9 nmol/l.

3 . The method according to claim 1 , wherein the therapeutic fluid is a starch solution.

4 . The method according to claim 1 , wherein the therapeutic fluid is an albumin solution.

5 . The method according to claim 1 , wherein the therapeutic fluid is a gelatin solution.

6 . The method according to claim 1 , wherein the fluid therapy is administered intravenously to the patient.

7 . The method according to claim 1 , in which the method is performed by the use of a kit, said kit comprising:
detection reagents for determining the level of proADM or fragment(s) thereof in a sample from a subject, reference data, corresponding to high, intermediate and/or low severity levels of proADM, wherein a low severity level of proADM or fragment(s) thereof is below 2.75 nmol/l, wherein an intermediate severity level of proADM or fragment(s) thereof is from 2.75 nmol/l to 10.9 nmol/l, and wherein a high severity level of proADM or fragment(s) thereof is above 10.9 nmol/l, wherein said reference data is stored on a computer readable medium and/or employed in the form of computer executable code configured for comparing the determined levels of proADM or fragment(s) thereof, and a pharmaceutical composition comprising a therapeutic fluid.

8 . The method according to claim 1 , wherein the patient has been diagnosed as having sepsis, severe sepsis or septic shock.

9 . The method according to claim 1 , wherein the patient has been diagnosed as having one or more organ failure(s), or wherein the patient is a patient suffering from traumatic injuries or polytrauma or a postsurgical patient, or any combination thereof.

10 . The method according to claim 1 , wherein the fluid therapy administered to the patient after the sample was obtained from the patient, comprises administration of a colloid solution.

11 . The method according to claim 1 , wherein the fluid therapy, administered to the patient after the sample was obtained from the patient, comprises administration of a crystalloid solution.

12 . The method according to claim 1 , wherein the patient receives fluid therapy and
administering at most 2.78 ml/kg of body weight of fluid wherein fluid is administered to the patient within approximately 24 hours if a low severity level of proADM or fragment(s) thereof is determined in the sample, administering at most 4.2 ml/kg of body weight of fluid to the patient within approximately 24 hours if an intermediate severity level of proADM or fragment(s) thereof is determined in the sample, or administering at most 9.95 ml/kg of body weight of fluid to the patient within approximately 24 hours if a high severity level of proADM or fragment(s) thereof is determined in the sample, and wherein a low severity level of proADM or fragment(s) thereof is below 2.75 nmol/l, wherein an intermediate severity level of proADM or fragment(s) thereof is from 2.75 nmol/l to 10.9 nmol/l, and wherein a high severity level of proADM or fragment(s) thereof is above 10.9 nmol/l.

13 . A method for treating a patient comprising:
administering to said patient a pharmaceutical composition comprising a therapeutic fluid, wherein the administered composition is adjusted or not adjusted by a method, which comprises obtaining a sample from said patient, determining a level of pro adrenomedullin (proADM) or fragment(s) thereof in said sample, wherein a low severity level of proADM or one or more fragments thereof is below 2.75 nmol/l, wherein an intermediate severity level of proADM or one or more fragments thereof is from 2.75 nmol/l to 10.9 nmol/l, and wherein a high severity level of proADM or one or more fragments thereof is above 10.9 nmol/l, and wherein a level of proADM or fragment(s) thereof in a first and a second sample from the patient has been determined, wherein the second sample is obtained after obtaining the first sample; wherein when in the first sample a low or intermediate severity level of proADM or fragment(s) thereof has been determined and an increase in the levels of proADM or fragment(s) thereof from low to intermediate severity or from intermediate to high severity is determined in the second sample compared to the first sample, a reduction in the volume, frequency and/or rate of fluid is administered to the patient, or wherein when in the first sample a high severity level of proADM or fragment(s) thereof has been determined, and no change in the levels of proADM or fragment(s) thereof is determined in the second sample compared to the first sample, such that a high severity level is maintained a reduction in the volume, frequency and/or rate of fluid is administered to the patient, or wherein when in the first sample a low severity level of proADM or fragment(s) thereof has been determined, and no increase in the levels of proADM or fragment(s) thereof is determined in the second sample compared to the first sample, such that the low severity level is maintained, the volume, frequency and/or rate of fluid administered to the patient is not adjusted.

14 . The method according to claim 13 , comprising
reducing the volume and/or rate of fluid to be administered to the patient upon an increase from a low to an intermediate or high severity level of proADM or fragment(s) thereof, or an increase from an intermediate to a high severity level of proADM or fragment(s) thereof, wherein a low severity level of proADM or fragment(s) thereof is below 2.75 nmol/l, an intermediate severity level of proADM or fragment(s) thereof is from 2.75 nmol/l to 10.9 nmol/l, and a high severity level of proADM or fragment(s) thereof is above 1

Assignees

• Brahms Gmbh

Inventors

• Wilson Darius

Classifications

• A61K49/0004

  Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions · CPC title

• G01N2800/26

  Infectious diseases, e.g. generalised sepsis · CPC title

• G01N2333/575

  Hormones · CPC title

• G01N2800/56

  Staging of a disease; Further complications associated with the disease · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title