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

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