Clinical trial NCT04028505: Terlipressin Infusion in Variceal Hemorrhage
Official title: Terlipressin Bolus Versus Continuous Infusion in Patients With Variceal Hemorrhage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Terlipressin Adverse Reaction
Keywords: Terlipressin Drug
Continuous Infusion
Bolus Form
Lead sponsor: Aga Khan University
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
First posted: 2019-07-22
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental Arm: Standard of care being given at AKUH + Continuous infusion of Terlipressin at a rate of 0.5mg/hour for the first 24 hours Comparator Arm: Standard of care being given at AKUH + Bolus infusion of Terlipressin at a frequency of 2mg every six hourly for first 24 hours
Primary purpose: TREATMENT

Brief summary: Randomized, open label study of intravenous terlipressin infusion vs. bolus for the treatment of variceal hemorrhage. 24 hour regimen consisting of intravenous terlipressin will be used either at a rate of 0.5mg/hour or 2mg bolus every 4 hourly. Participants will be randomized into intervention and control arm using block randomization by computer generated random numbers. Efficacy will be assessed by clinical improvement in symptoms and signs of GI bleed. To assess safety, frequency and degree of adverse reactions will be observed. Periodic assessments until 5 days will be done consisting of physical examination, safety assessments, vital signs and lab tests.

Detailed description: Randomized, open label trial, conducted on patients admitted with acute variceal hemorrhage at The Aga Khan University Hospital, Karachi (AKUH). Patients will be followed in clinic after discharge to assess survival for 6 weeks.

Intravenous terlipressin will be obtained from Clinical Trials Unit, AKUH pharmacy in standard IV infusion form. Following complete clinical and laboratory evaluation, assessing the patient for eligibility, informed consent will be obtained from all the participants who are willing to be part of this study. After obtaining the informed consent, study participants will be randomized into the intervention arm (continuous infusion of Terlipressin) or the control arm (bolus form of Terlipressin). Participants who are randomized to the intervention arm will be administered a continuous infusion of Terlipressin at a rate of 0.5mg/hour for the first 24 hours. Participants randomized into the control group will be administered a bolus form of Terlipressin at a rate of 2mg every six hourly for the first 24 hours respectively. In case of weekends/public holidays intravenous terlipressin will be obtained from the main pharmacy of AKUH.

The trial will be conducted in in-patient units of AKUH where eligible patients are admitted. It may include emergency room, special care unit and general ward. Moreover, patients will be followed up by phone calls and in outpatient's clinics to assess survival six weeks post discharge.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 to 60 years
2. Either gender
3. A diagnosis of liver cirrhosis;
4. Initial presentation with acute gastroesophageal variceal bleeding
5. Willing to provide informed consent to participate in the study (by study subject or next of kin)

Exclusion Criteria:

1. Age \< 18 or \> 60 years
2. Not willing to provide consent due to any reason
3. No liver cirrhosis
4. Acute upper gastrointestinal bleeding unrelated to varices;
5. Use of somatostatin or octreotide.
6. Hepatocellular Carcinoma (HCC)outside Milan's criteria
7. Advance cardiovascular, pulmonary or renal disease (e.g. asthma, hypertension, arrhythmia, renal insufficiency)
8. History of hypersensitivity to Terlipressin
9. Pregnancy
10. Patients already admitted at AKUH who develop upper GI bleed during admission.

Primary outcomes:
measure: Reduction in tachycardia, measured through heart rate (>100 bpm) being displayed in the electronic monitors in wards, emergency room and out-patient clinics
timeFrame: 6 weeks (Overall length of follow-up)
measure: Improvement in mean arterial pressure, being displayed in the electronic monitors in wards, emergency room and out-patient clinics
timeFrame: 6 weeks (Overall length of follow-up)
measure: In-patient hospital mortality, assessed through medical records.
timeFrame: Admission of patient till death in the hospital
measure: Failure to control bleeding as assessed by physiological parameters in the blood
timeFrame: Admission of patient till discharge from the hospital
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: 6 weeks (Overall length of follow-up)
Secondary outcomes:
measure: Out of hospital mortality assessed through telephonic interviews from patient's caregiver
timeFrame: 5 weeks after being discharged from the hospital
measure: Failure to control bleeding as assessed by physiological parameters in the blood
timeFrame: 5 weeks after being discharged from the hospital
measure: Prolong hospital stay (> 5 days) as assessed through medical records and pre-designed questionnaire
timeFrame: 5 days after admission till being discharged from the hospital
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Aga Khan University Hospital
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Shahab Abid, PhD,FRCP
role: PRINCIPAL_INVESTIGATOR
References: