Terlipressin Infusion in Variceal Hemorrhage

Terlipressin Adverse Reaction Clinical Trial

— TT  

Official title:

Terlipressin Bolus Versus Continuous Infusion in Patients With Variceal Hemorrhage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04028505
• Other study ID #: 5209-Med-ERC-18
• Status: Recruiting
• Phase: Phase 3
• Start date: October 25, 2018
• Est. completion date: October 25, 2020

Study information

• Verified date: July 2019
• Source: Aga Khan University
• Contact: Shahab Abid, Phd,FRCP
• Phone: +92213486
• Email: shahab.abid[@]aku.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: October 25, 2020
• Est. primary completion date: April 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemorrhage
• Terlipressin Adverse Reaction

Intervention

Drug:
• Terlipressin Injectable Product
Intravenous terlipressin will be obtained from Clinical Trials Unit, AKUH pharmacy in standard IV infusion form. 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.

Locations

Country	Name	City	State
Pakistan	Aga Khan University Hospital	Karachi	Sindh

Sponsors (2)

Lead Sponsor	Collaborator
Aga Khan University	Mallinckrodt

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in tachycardia, measured through heart rate (>100 bpm) being displayed in the electronic monitors in wards, emergency room and out-patient clinics	It will be assessed by trained research coordinator as; the number of study participants with 20% reduction in tachycardia as compared to the baseline between the two arms.	6 weeks (Overall length of follow-up)
Primary	Improvement in mean arterial pressure, being displayed in the electronic monitors in wards, emergency room and out-patient clinics	It will be assessed by trained research coordinator as; the number of study participants with 20% improvement in mean arterial pressure as compared to the baseline between the two arms.; Adverse events related to terlipressin, such as hyponatremia, diarrhea, abdominal pain; arterial hypertension should be reported to the primary gastroenterologist between the two arms.	6 weeks (Overall length of follow-up)
Primary	In-patient hospital mortality, assessed through medical records.	It will be assessed through medical records, by a trained research coordinator as the number of study participants dying within the hospital between the two arms.	Admission of patient till death in the hospital
Primary	Failure to control bleeding as assessed by physiological parameters in the blood	It will be assessed by a trained research coordinator as the number of participants having fresh hematemesis and 3 gm drop in hemoglobin (9% drop in hematocrit) within a 24 hours' time period between the two arms.	Admission of patient till discharge from the hospital
Primary	Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	It will be assessed by trained research coordinator as; the number of participants having experienced any adverse events such as hyponatremia, diarrhea, abdominal pain, arterial hypertension, 5 days after having terlipressin drug, between the two arms.	6 weeks (Overall length of follow-up)
Secondary	Out of hospital mortality assessed through telephonic interviews from patient's caregiver	It will be assessed by trained research coordinator as; the number of participants dying after being discharged from the hospital between the two arms within the follow-up time period of the study.	5 weeks after being discharged from the hospital
Secondary	Failure to control bleeding as assessed by physiological parameters in the blood	It will be assessed by trained research coordinator as the number of participants having fresh hematemesis and 3 gm drop in hemoglobin (9% drop in hematocrit) after being discharged from the hospital till three subsequent follow-up visits between the two arms.	5 weeks after being discharged from the hospital
Secondary	Prolong hospital stay (> 5 days) as assessed through medical records and pre-designed questionnaire	It will be assessed by trained research coordinator as; the number of participants having stayed in the hospital for more than five days between the two arms.	5 days after admission till being discharged from the hospital