Heparin to Prevent Organ Failure in Acute Pancreatitis

Official title

Unfractionated Heparin for Organ Failure Prevention in Acute Pancreatitis: A Randomized Trial

Overview

This clinical trial is designed to evaluate whether adding a standard blood-thinning medication, Unfractionated Heparin, to standard hospital care can help prevent severe organ failure in patients admitted with acute pancreatitis. Acute pancreatitis is a sudden and severe inflammation of the pancreas. During this condition, intense inflammation can trigger a hypercoagulable state (excessive blood clotting) in the small blood vessels supplying vital organs. This microvascular clotting can block normal blood flow, starving tissues of oxygen and potentially leading to dangerous, life-threatening multi-organ failure involving the lungs, kidneys, or heart. Currently, standard medical care for acute pancreatitis is purely supportive-consisting of intensive intravenous fluid hydration, pain management, and nutritional support-without any specific targeted drug therapy to halt the disease's progression. In this study, participating patients are randomly assigned into one of two balanced groups using a randomized lottery method upon their admission to the surgical unit: 1. The Control Group: Receives standard supportive hospital medical care only. 2. The Intervention Group: Receives the same standard supportive medical care plus a continuous, carefully monitored intravenous infusion of Unfractionated Heparin. The primary objective of the study is to determine if early initiation of this standard anticoagulant therapy preserves blood flow, dampens the severe inflammatory cascade, and successfully prevents the development of new or worsening organ failure. The study will also evaluate secondary clinical endpoints, including the total duration of the patient's hospital stay and the general safety profile of the intervention by monitoring for any adverse bleeding complications.

Detailed description

This randomized controlled clinical trial is conducted to evaluate the clinical efficacy and safety of early, continuous intravenous administration of Unfractionated Heparin (UFH) as an adjunctive treatment to mitigate the development and progression of systemic multi-organ failure in patients presenting with acute pancreatitis.

Clinical Workflow and Protocol:

1. Patient Screening and Enrollment:

Patients presenting to the emergency department or the surgical wards with a clinical diagnosis of acute pancreatitis are assessed immediately for eligibility based on pre-established clinical parameters. Acute pancreatitis is diagnosed using standard clinical criteria, requiring at least two of the following: characteristic severe abdominal pain, serum amylase or lipase levels elevated to at least three times the upper limit of normal, or characteristic cross-sectional abdominal imaging findings. 2. Baseline Assessments:

Upon securing formal written informed consent, enrolled patients undergo an immediate baseline clinical evaluation. Baseline laboratory parameters-including a complete blood count (CBC), serum electrolytes, renal function tests (serum creatinine and blood urea), liver function tests, serum amylase/lipase, and arterial blood gases (ABGs)-are drawn. Baseline physiological parameters are recorded to calculate initial disease severity and multi-organ function scores. 3. Randomization and Group Allocation:

Following baseline verification, patients are randomly allocated in a 1:1 ratio to either the Intervention Group (Group A) or the Control Group (Group B) utilizing a randomized lottery method managed through sequentially numbered, opaque, sealed envelopes to ensure allocation concealment. 4. Therapeutic Interventions:

* Control Group (Group B): Patients receive standard institutional supportive medical therapy for acute pancreatitis. This includes aggressive tailored intravenous fluid resuscitation (primarily balanced crystalloids like Ringer's Lactate) titrated to clinical endpoints, standardized analgesia for pain management, close hemodynamic monitoring, and early targeted nutritional support. * Intervention Group (Group A): Patients receive the identical standard institutional supportive medical therapy protocol provided to the control group. In addition, an active anticoagulant protocol is initiated within the first 24 hours of admission, consisting of Unfractionated Heparin administered via a continuous intravenous infusion pump. 5. Safety Monitoring and Titration:

To maximize patient safety and evaluate potential adverse events, patients receiving the intravenous UFH protocol undergo rigorous monitoring. Coagulation profiles, including Activated Partial Thromboplastin Time (aPTT), are checked regularly to guide safe administration. Patients in both groups are carefully monitored daily by the clinical team for any clinical signs of minor or major bleeding complications, such as hematemesis, melena, epistaxis, or an unexplained drop in hemoglobin levels. 6. Outcome Evaluation:

All participating patients are evaluated daily throughout their acute hospital stay. The development of systemic complications is tracking objectively using the Modified Marshall Scoring System, which grades respiratory, cardiovascular, and renal organ function daily from admission through Day 14 or until official hospital discharge. Total duration of hospital stay and all-cause clinical outcomes are recorded at the time of discharge.

Interventions

• Drug Unfractionated heparin
  * Route: Continuous intravenous (IV) infusion via a calibrated pump or micro-drip controller to maintain stable serum drug levels. * Timing: Initiated within the first 24 hours of hospital admission, immediately following the clinical diagnosis of acute pancreatitis on the surgical ward. * Dosing: Administered as a continuous weight-adjusted maintenance infusion titrated per institutional safety guidelines for non-cardiac anticoagulation. No loading bolus is given. * Duration: Maintained continu
• Other Standard supportive care
  Standard institutional supportive medical therapy for acute pancreatitis, including intravenous fluid resuscitation (Ringer's Lactate), standardized analgesia for pain management, close clinical monitoring, and early nutritional support. No anticoagulant infusions will be administered.

Primary outcome measures

• Incidence of New-Onset Organ Failure [Time frame: Daily from Day 1 (after baseline assessment at hospital admission) up to Day 7 of hospitalization or until official hospital discharge, whichever occurs first.]

Eligibility criteria

Inclusion criteria

• Patients aged 18 years or older.
• Confirmed clinical diagnosis of acute pancreatitis based on meeting at least two of the following three revised Atlanta criteria: (1) acute onset of severe, persistent upper abdominal pain; (2) serum amylase or lipase levels elevated to at least three times the upper limit of normal; (3) characteristic findings of acute pancreatitis on cross-sectional abdominal imaging.
• Presentation to the hospital and initiation of the trial protocol within 24 hours of the onset of symptoms.
• Absence of systemic organ failure at the baseline assessment during initial hospital admission.

Exclusion criteria

• Baseline organ failure already present at the time of initial hospital admission (defined as a Modified Marshall Score of 2 or more in any organ system).
• Patients with a known history of chronic pancreatitis or recurrent episodes of pancreatitis.
• History of hypersensitivity, allergy, or known adverse reactions to heparin, low molecular weight heparins, or related anticoagulants.
• Active clinically significant bleeding, recent major hemorrhage, known bleeding diathesis, or severe thrombocytopenia (platelet count less than 100,000/mcL).
• Existing indication for therapeutic systemic anticoagulation (such as active deep vein thrombosis, pulmonary embolism, mechanical heart valves, or atrial fibrillation).
• Pregnant or lactating females.
• Refusal to provide informed consent to participate in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Pakistan · 1 center

• Allied Hospital, Faisalabad — Faisalābad

Publications

• Tozlu M, Kayar Y, Ince AT, Baysal B, Senturk H. Low molecular weight heparin treatment of acute moderate and severe pancreatitis: A randomized, controlled,open-label study. Turk J Gastroenterol. 2019 Jan;30(1):81-87. doi: 10.5152/tjg.2018.18583. PMID 30289392

Identifiers

NCT: NCT07609771 · 48.ERC/FMU/2024-25/208

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗