Investigating FE 202158 as Potential Primary Treatment in Patients With Early Septic Shock

• ClinicalTrials.gov Identifier: NCT01612676
• Recruitment Status: Completed
• First Posted: June 6, 2012
• Results First Posted: January 16, 2017
• Last Update Posted: March 23, 2017
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

Study Description

Brief Summary:

The purpose of this trial is to investigate the potential of FE 202158 as a treatment which can stabilize blood pressure for treatment of patients in early septic shock.

Condition or disease	Intervention/treatment	Phase
Septic Shock	Drug: FE 202158	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Feasibility Trial Investigating FE 202158 as Potential Primary Vasopressor Treatment in Patients With Vasodilatory Hypotension in Early Septic Shock.
• Study Start Date: June 2012
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: November 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Drug; FE 202158	Drug: FE 202158

Outcome Measures

Primary Outcome Measures :

1. Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine [ Time Frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. ]
   Mean arterial pressure (MAP) was measured intra-arterially on a continuous basis. Success percentage of patients maintaining target/adequate MAP (>60 mmHg) without norepinephrine is presented.
2. Cumulative Dose of FE 202158 [ Time Frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. ]
   Cumulative dose of FE 202158 was calculated from Day 1 up to Day 7.
3. Infusion Rate of FE 202158 [ Time Frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. ]
   Infusion rate of FE 202158 was presented from Day 1 up to Day 7.
4. Cumulative Dose of Norepinephrine [ Time Frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. ]
   Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Cumulative dose of norepinephrine was calculated from Day 1 up to Day 7.
5. Infusion Rate of Norepinephrine [ Time Frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. ]
   Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Infusion rates and all changes in infusion rates of norepinephrine were recorded continuously during the 7 day maximum treatment period.
6. Time to Septic Shock Resolution [ Time Frame: Day 1 up to Day 28 ]

   The Kaplan-Meyer estimation of time to out of septic shock was estimated where time to (first) septic shock resolution was defined as time of end of infusion regimen. Intermittent off treatment periods were regarded as part of the shock duration.

   Time to all but one patient out of septic shock is presented.

Secondary Outcome Measures :

1. Urinary Output [ Time Frame: Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. ]
   The urinary output was recorded every 24 hours up to Day 7, or as long as the patient was in intensive care unit.
2. Fluid Balance [ Time Frame: Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. ]
   The fluid balance (accumulated input/output) was recorded in 24-hour collecting periods when the patient was in the intensive care unit and during the infusion of FE 202158.
3. Summary of Investigator Reported Outcomes [ Time Frame: Day 1 up to Day 2 ]
   Investigator reported outcome on FE 202158 performance. Answers were graded on a visual analogue scale (VAS) from 0 to 10, 0 being the worst and 10 being the best outcome.
4. Morbidity Assessment [ Time Frame: Day 1 up to Day 28 ]
   Percentage of all the "Days alive and out/free of" intensive care unit, hospital, dialysis, or ventilation within Day 28 were summarized. Patients dying before or at Day 28 were counted as zero.
5. Graded Morbidity [ Time Frame: Day 1 up to Day 28 ]
   Collection of data on graded morbidity was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital.
6. Mortality [ Time Frame: Day 1 up to Day 28 ]
   Collection of data on mortality was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital.
7. Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram [ Time Frame: Day 1 up to Day 7, and at follow-up assessments performed 24-72 hours after end of IMP infusion ]
   Significant changes for vital signs (blood pressure, heart rate, mean arterial pressure), electrocardiogram (ECG), and laboratory parameters (clinical chemistry, haematology, haemostasis, and urinary parameters).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed informed consent form by the patient or a legal representative according to local regulations'
• Man or women 18 years of age or older
• Body weight below 115 kg for male patients and 100 kg for female patients
• Proven or suspected infection
• Septic shock, i.e. vasodilatory hypotension requiring vasopressor support
• Willing to use an adequate barrier method or hormonal method of contraception, if not abstinent, from informed consent to one week after the end of infusion of study medication

Exclusion Criteria:

• Present or a history within the last 6 months of symptoms of acute coronary syndrome (myocardial infarction or unstable angina)
• Known or suspected endocarditis
• Hypovolaemia suspected on clinical grounds, e.g. cold extremities with delayed capillary filling, low cardiac filling pressure, marked systolic or pulse pressure variation or positive leg raising test
• Known or suspected cardiac failure
• Known or suspected infection with (HIV)-1, HIV-2, hepatitis B, or hepatitis C
• Pregnancy or breastfeeding
• Any cause of hypotension other than early septic shock
• Use of vasopressin or terlipressin within 7 days prior to start of IMP infusion
• Proven or suspected acute mesenteric ischemia, as judged by the investigator
• Known episode of septic shock within 1 month prior to screening
• Death anticipated within 24 hours, or due to the underlying disease within 3 months
• Known past or current 2nd and 3rd degree AV-block without a well functioning pacemaker
• Brain injury within current hospitalisation
• Present hospitalisation with burn injury
• Symptomatic peripheral vascular disease including Raynaud's syndrome
• Previously included in this trial
• Intake of an Investigational Medicinal Product (IMP) within the last 3 months (or longer if judged by the Investigator to possibly influence the outcome of the current study)
• Known participation in another interventional clinical trial
• Considered by the investigator to be unsuitable to participate in the trial for any other reason

Contacts and Locations

Locations

Belgium

Erasme Hospital Free University of Brussels

Brussels, Belgium

Saint-Luc University Hospital

Brussels, Belgium

University Hospital Brussels

Brussels, Belgium

Denmark

Hvidovre Hospital

Hvidovre, Denmark

Sponsors and Collaborators

Ferring Pharmaceuticals

Investigators

• Study Director: Clinical Development Support; Ferring Pharmaceuticals

More Information

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01612676
• Other Study ID Numbers: 000025; 2012-001254-26 ( EudraCT Number )
• First Posted: June 6, 2012
• Results First Posted: January 16, 2017
• Last Update Posted: March 23, 2017
• Last Verified: February 2017

Additional relevant MeSH terms:

Shock, Septic; Shock; Pathologic Processes; Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation