Cafedrin/Theodrenalin (Akrinor®) Versus Ephedrine for Treatment of Hypotension in the Peri-operative Phase in Inpatient Setting

• ClinicalTrials.gov Identifier: NCT02893241
• Recruitment Status: Completed
• First Posted: September 8, 2016
• Last Update Posted: March 20, 2018
• Sponsor: Ratiopharm GmbH
• Information provided by (Responsible Party): Teva Pharmaceutical Industries ( Ratiopharm GmbH )

Tracking Information

• First Submitted Date: September 2, 2016
• First Posted Date: September 8, 2016
• Last Update Posted Date: March 20, 2018
• Actual Study Start Date: April 30, 2016
• Actual Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 16, 2018)

• The incidence of newly occurring HR ≥ 100 beats/min [ Time Frame: during the first 15 minutes after initial drug administration of cafedrine/theodrenaline or ephedrine ]
• Weighted deviation below the individually determined, lowest systolic blood pressure BPmin [ Time Frame: within the first 15 minutes after the initial delivery of the antihypotonic drug as area1 (AUC) between the systolic blood pressure curve (below BPmin) and the lower limit BPmin ]

Original Primary Outcome Measures (submitted: September 2, 2016)

• The incidence of HR ≥ 100 beats/min [ Time Frame: during the first 15 minutes after initial drug administration of cafedrine/theodrenaline or ephedrine ]
• Weighted deviation below the individually determined, lowest systolic blood pressure BPmin [ Time Frame: within the first 15 minutes after the initial delivery of the antihypotonic drug as area1 (AUC) between the systolic blood pressure curve (below BPmin) and the lower limit BPmin ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cafedrin/Theodrenalin (Akrinor®) Versus Ephedrine for Treatment of Hypotension in the Peri-operative Phase in Inpatient Setting
• Official Title: Cafedrin/Theodrenalin (Akrinor®) Versus Ephedrine for Treatment of Hypotension in the Peri-operative Phase in Inpatient Setting: a Multicenter, Prospective, Non-interventional Study
• Brief Summary: This is a national, multicentre, prospective, open, two-arm, non-interventional study with hospitalized patients, who are treated routinely with cafedrine/theodrenaline or ephedrine after occurrence of perioperative hypotension, wherein the patients are assigned to a treatment arm based on the department.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Hospitalized patients, who are treated routinely with cafedrine/theodrenaline or ephedrine after occurrence of perioperative hypotension,
• Condition: Hypotension

Intervention

• Drug: Cafedrine/theodrenaline
• Drug: Ephedrine

Study Groups/Cohorts

• Cohort A
  Patients ≥ 50 years old, with pre-existing comorbidities, who receive general anaesthesia
  Interventions:

  • Drug: Cafedrine/theodrenaline
  • Drug: Ephedrine
• Cohort B
  Patients, who undergo caesarean section under spinal anaesthesia
  Interventions:

  • Drug: Cafedrine/theodrenaline
  • Drug: Ephedrine

• Publications *: Eberhart L, Geldner G, Huljic S, Marggraf K, Keller T, Koch T, Kranke P. A non-interventional comparative study of the 20:1 combination of cafedrine/theodrenaline versus ephedrine for the treatment of intra-operative arterial hypotension: the 'HYPOTENS' study design and rationale. Curr Med Res Opin. 2018 Jun;34(6):953-961. doi: 10.1080/03007995.2018.1438379. Epub 2018 Feb 28.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 16, 2018): 2013
• Original Estimated Enrollment (submitted: September 2, 2016): 1870
• Actual Study Completion Date: December 31, 2017
• Actual Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Inpatients, who received IV treatment (bolus administration) with cafedrine/theodrenaline or ephedrine (Ephedrin Meduna) due to an acute arterial hypotension
• Consent to use of data is available
• Patient under careful blood pressure and pulse monitoring (at least 2 minutes measuring interval (BP/HR) and/or at least 7 measurements within the first 15 minutes after the first application of cafedrine/theodrenaline or ephedrine)

Cohort A:

• Treatment of hypotension in < 100 mm Hg syst. and/or drop in blood pressure > 20% syst. compared to preoperative base value (syst.)
• Patients ≥ 50 years old
• Pre-existing comorbidities (ASA classification 2-4)
• Elective surgery
• General anaesthesia with propofol/fentanyl ≥ 0.2 mg (or equivalent)

Cohort B:

• Treatment of hypotension in < 100 mm Hg syst. and/or drop in blood pressure > 10% syst. compared to preoperative base value (syst.)
• Patients ≥ 18 years old
• Caesarean section under spinal anaesthesia

Exclusion Criteria:

• Contraindication to the use of cafedrine/theodrenaline or ephedrine (Ephedrin Meduna) in accordance with current German specialist information

  • Hypersensitivity to any product ingredient
  • Hypertensive blood pressure readings
  • Mitral stenosis
  • Narrow-angle glaucoma
  • Hyperthyroidism
  • Pheochromocytoma
  • Prostatic adenoma with urinary retention
  • Bronchial asthmatics with sulphite sensitivity
  • Hyper-excitability
  • Arteriosclerosis
  • Aneurysm
  • Treatment with other indirect sympathomimetic drugs (Example: phenylpropanolamine, phenylephrine, pseudoephedrine or methylphenidate)
  • Use of Monoamine oxidase (MAO) inhibitors (including within the last two weeks)
• Prophylactic administration of cafedrine/theodrenaline or ephedrine or other anti-hypertensives
• Sepsis, septic shock or systemic inflammatory response syndrome (SIRS)

Cohort A:

• Intra-cranial surgery or heart surgery

Cohort B:

• High-risk pregnancy (emergency Caesarean, severe infantile malformation)
• Multiple pregnancy
• Amniotic infection syndrome

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02893241
• Other Study ID Numbers: TV48531-CV-40092
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Teva Pharmaceutical Industries ( Ratiopharm GmbH )
• Study Sponsor: Ratiopharm GmbH
• Collaborators: Not Provided

Investigators

• Study Director: Teva Medical Expert, MD; Teva Pharmaceuticals USA

• PRS Account: Teva Pharmaceutical Industries
• Verification Date: March 2018