Single Dose Administration of Alpha-1 Anti-Trypsin for the Amelioration of Organ Injury in Patients Undergoing Cardiac Surgery

NCT02191839 | Unknown Phase 1 DMC

• 1 other identifier: SOR 133-13 ctil
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

Protocol Summary STUDY DESIGN A pilot, prospective, double blind, randomized, placebo controlled study. STUDY POPULATION Patients assigned to elective CABG with cardiopulmonary bypass (CPB) at the Department of Cardiothoracic Surgery, Soroka University Medical Center. OBJECTIVE To evaluate anti-inflammatory effects, effects on organ function preservation, and postoperative blood loss reduction following AAT-1 administration in patients undergoing CABG with CPB. PRIMARY ENDPOINT Postoperative organ function preservation and blood loss following preoperative single-dose AAT-1 administration. SAMPLE SIZE CONSIDERATIONS A cohort of 20 patients will be recruited. Patients will be randomized to receive either AAT-1 or placebo prior to surgery. Whereas this is a proof of concept pilot study, statistical significance is not the primary objective. INCLUSION CRITERIA 1. The study population will comprise patients between 40 and 70 years of age, irrespective of gender, at low or intermediate operative risk (calculated Logistic Euroscore stratification of 5% or less), assigned to elective CABG with CPB. Recruitment depending on patients informed consent. EXCLUSION CRITERIA Co-existing conditions including:

1. 1.Coagulation abnormalities
2. 2.Severe pulmonary disease defined by blood oxygen saturation of 90% or less or FEV1 of less than 60% of predicted.
3. 3.Renal dysfunction defined be serum creatinine levels higher or equal to 1.8 mg%,
4. 4.Abnormal liver function tests
5. 5.Uncontrolled diabetes mellitus,
6. 6.Severe peripheral vascular disease
7. 7.Prior cerebrovascular neurological event.
8. 8.Abnormal left or right ventricular function.
9. 9.Treatment with warfarin or thienopyridine class of anti platelet agents.

Conditions

Post Cardiac Surgery Systemic Inflammatory Response

Keywords

cardiac surgery; alpha 1 antitrypsin; inflammation; post operative bleeding; organ function

Outcome Measures

Primary Outcomes (7)

• post operative inflammatory response

  1\. The occurrence and magnitude of systemic inflammatory response and organ dysfunction will be recorded and quantified by laboratory markers. Related laboratory markers will be monitored on a daily basis during the recovery period (in the intensive care unit and at the ward).

  post operative day 1-5

• Pulmonary function:

  Pulmonary function will be evaluated by measured overall mechanical ventilation time, peak inspiratory pressures (PIP), plateau pressures, physiologic dead space and static and dynamic lung compliance. Bronchoalveolar lavage (BAL) will be performed 3 hours after operation (while the patient is anesthetised and intubated) and extracted fluid will be analyzed for inflammatory markers. A-a DO2 calculation \[AaDO2 = (713 x FiO2) - (pCO2 / 0.8) - (paO2)\] will be measured daily. Complete pulmonary function test will be performed before and 4 days after the operation. Chest radiographs will be evaluated and quantified by an independent radiologist for the occurrence of atelectasis, pulmonary edema, or pleural changes.

  post op day 1-5

• Renal function:

  Daily measurements of urine output, serum creatinine levels, creatinine clearance and urinary albumin levels. Acute kidney injury (AKI) markers will be sampled in the ICU.

  post op day 1-5

• Brain injury assessment:

  The degree of insult to the brain will be measured by plasma S-100 proteinlevels. Assessment of damage to the blood-brain barrier (BBB) will be performed by magnetical resonance imaging (MRI) modality

  post op day 1-5

• Hepatic function:

  Daily measurements of serum hepatic enzymes levels.

  post op day 1-5

• Cardiac function:

  Monitoring of cardiac enzymes levels; need and magnitude of required inotrope treatment; occurrence of low cardiac output syndrome (defined as systolic blood pressure of 90 mmHg or less coupled with central venous pressure (CVP) of 15 mmHg or more) and incidence of cardiac arrhythmias. Transthoracic echocardiography examination will be performed on postoperative day 5 and assessed by an independent cardiologist.

  post op day 1-5

• Blood loss:

  Operative and postoperative blood loss will be monitored as well as daily hemoglobin levels. Daily platelet counts and thromboelastograms will be performed. The distribution of blood products and total administered will be recorded daily. Postoperative CRP levels will be evaluated daily.

  post op day 1-2

Study Arms (2)

alpha 1 antitrypsin

ACTIVE COMPARATOR

patients receive 4 grams of IV alpha 1 antitrypsin preoperatively

Drug: Alpha 1-Antitrypsin

placebo

PLACEBO COMPARATOR

10 patients will randomely receive placebo

Interventions

Alpha 1-Antitrypsin DRUG

alpha 1 antitrypsin

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. The study population will comprise patients between 40 and 70 years of age, irrespective of gender, at low or intermediate operative risk (calculated Logistic Euroscore stratification of 5% or less), assigned to elective CABG with CPB. Recruitment depending on patients informed consent.

You may not qualify if:

• Co-existing conditions including:
• Coagulation abnormalities
• Severe pulmonary disease defined by blood oxygen saturation of 90% or less or FEV1 of less than 60% of predicted.
• Renal dysfunction defined be serum creatinine levels higher or equal to 1.8 mg%,
• Abnormal liver function tests
• Uncontrolled diabetes mellitus,
• Severe peripheral vascular disease
• Prior cerebrovascular neurological event.
• Abnormal left or right ventricular function.
• Treatment with warfarin or thienopyridine class of anti platelet agents -

Sponsors & Collaborators

• Soroka University Medical Center: lead

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency; Inflammation

Interventions

alpha 1-Antitrypsin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Study Officials

• DAN ABRAHAMOV, DR

  Soroka University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

DAN ABRAHAMOV, DR

CONTACT

972504506205; danab3@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: July 7, 2014
• First Posted: July 16, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 16, 2014

Record last verified: 2014-07