Phase I Study of Vasoactive Intestinal Peptide in Patients With Acute Respiratory Distress Syndrome and Sepsis
Phase I Study of Vasoactive Intestinal Peptide in Patients With Acute Respiratory Distress Syndrome and Sepsis
OBJECTIVES:

 I. Determine the maximum tolerated dose of vasoactive intestinal peptide in patients with
 acute respiratory distress syndrome.

 II. Evaluate the safety and pharmacodynamic activity of this peptide in these patients.
PROTOCOL OUTLINE:

 This is a dose escalation study.

 Patients receive vasoactive intestinal peptide (VIP) IV over either 6 or 12 hours.

 Cohorts of 3 patients each receive escalating doses of VIP over either 6 or 12 hours until
 the maximum tolerated dose is determined.

 Patients are followed for 30 days.
PROTOCOL ENTRY CRITERIA:

 --Disease Characteristics--

 Diagnosis of adult respiratory distress syndrome (ARDS) with sepsis

 ARDS characterized by: hypoxemia refractory to supplemental oxygen therapy, diffuse
 pulmonary infiltrates, no cardiogenic cause of pulmonary edema, and reduced pulmonary
 compliance

 Sepsis characterized by: Two or more of the following: Fever or hypothermia; Tachycardia;
 Tachypnea; WBC greater than 12,000/mm3 or less than 4,000/mm3 or immature neutrophils;
 Hypotension; Clinical suspicion of infection; Inadequate organ perfusion or organ
 dysfunction as demonstrated by: Acute deterioration in mental acuity (excluding sedatives
 or other nonsepsis causes) OR Unexplained metabolic acidosis OR Oliguria for greater than 2
 hours OR Unexplained coagulopathy (elevated PT or PTT or platelet count decreased to less
 than 50% of baseline within 24 hours or less than 100,000/mm3) OR Acute elevation of
 bilirubin to greater than 2.0 mg/dL AND elevation of alkaline phosphatase, SGOT, or SGPT

 No sepsis with unstable BP

 --Prior/Concurrent Therapy--

 At least 30 days since prior enrollment in investigational trial; No other concurrent
 enrollment in investigational trial

 --Patient Characteristics--

 Hematopoietic: See Disease Characteristics; No uncontrolled hemorrhage (transfusion of 4 or
 more units required within past 24 hours); No chemotherapy induced neutropenia (granulocyte
 count less than 1000/mm3)

 Hepatic: No severe liver disease with portal hypertension

 Renal: No anuria (urine output less than 50 mL/day)

 Cardiovascular: No cardiogenic shock

 Neurologic: No recent stroke, head trauma, or increased intracranial pressure; No other
 serious neurologic disorder

 Other: Not pregnant; No acquired immune deficiency syndrome; No immunosuppressed transplant
 patients; No severe burns; No irreversible underlying condition with rapidly fatal course;
 No marked obesity; No recent history of diarrhea