A Study to Systematically Assess the Efficacy and Safety of Intravenous Albumin Infusions in Severe POTS

NCT03365414 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: ZS-POTS-2017
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

POTS is a relatively common condition that affects millions of patients around the globe. It has an estimated prevalence of 170/100,000 with approximately 80% of patients being women of childbearing age. POTS is characterized by an excessive heart rate increase on assuming an upright posture, either standing or even sitting and leading to disabling palpitations, light-headedness, and even in syncope in severe cases. More than 95% patients with POTS have pronounced cardiovascular deconditioning and show marked exercise intolerance. The severity of POTS is variable. In mild cases the affected patient may continue with routine activities with minimal limitations. Severe form of the disease precludes most normal life activities, such as sitting upright, walking or standing to perform even basic house chores. An estimated 40% of patients with POTS have a resistant form of the condition that is nonresponsive or mildly responsive to all treatments resulting in continued functional limitations in the long term. Many of the currently available treatments in POTS are geared towards increasing blood pressure. These include compression stockings, increased daily fluid intake and increased salt ingestion. Saline infusions may be helpful in certain patients in the short term, though many do not respond. The effectiveness of medications varies greatly, with many patient failing to improve. A small series of clinical patients suffering from severe POTS have shown robust response to weekly albumin therapy, which supports the hypothesis that periodic albumin infusions will provide significant and sustained symptomatic relief to patients with severe POTS. This pilot study will explore the effectiveness of albumin infusions as a treatment for POTS. Eligible patients will receive weekly intravenous infusions of 5% Albumin or Saline in a double blinded fashion for 4 weeks and will crossover to the other infusion for 4 weeks after an intervening 4-week washout period. The participants will be required to maintain a daily diary of their symptoms during the screening, the study and washout periods. Any possible adverse effects as the result of infusions will be documented. Outcome measures will be quantified and validated at the end of each study period and the percentage reduction of tachycardia will be determined at the completion of each study arm.

Conditions

Postural Orthostatic Tachycardia Syndrome

Keywords

Postural Orthostatic Tachycardia Syndrome; POTS; Syncope; Vasovagal; Hypotension; Tachycardia

Outcome Measures

Primary Outcomes (1)

• Severity of Orthostatic Intolerance

  Self-reported severity of orthostatic intolerance assessed by the Orthostatic Symptom Grading Scale (OSGS) scores. Recorded daily. Each item is scored 0-4 (0= lowest severity; 4=greatest severity), yielding a total between 0 and 25.

  Change in Orthostatic Symptom Grading Scale (OSGS) scores from baseline to end of first arm (1-4 weeks), from end of washout (5-8 weeks) to end of second arm (9-12 weeks) and at end of study (16 week duration).

Secondary Outcomes (7)

• Disability Assessment

  Weekly through study completion, 16 week duration

• Degree of cardiovascular improvement - Heart rate

  Changes in heart rate (BPM) from baseline to end of first arm (1-4 weeks), from end of washout (5-8 weeks) to end of second arm (9-12 weeks) and at end of study (16 week duration).

• Degree of cardiovascular improvement - Pulse

  Changes in blood pressure (mm Hg) from baseline to end of first arm (1-4 weeks), from end of washout (5-8 weeks) to end of second arm (9-12 weeks) and at end of study (16 week duration).

• Change in maximal exercise capacity - Cardiopulmonary exercise testing

  Changes in aerobic capacity between baseline and end of first arm (1-4 weeks), and end of washout (5-8 weeks) to end of second arm (9-12 weeks). Follow-up data at end of study (16 week duration).

• Change in maximal exercise capacity - Electrocardiogram

  Changes in aerobic capacity between baseline and end of first arm (1-4 weeks), and end of washout (5-8 weeks) to end of second arm (9-12 weeks). Follow-up data at end of study (16 week duration).

Study Arms (2)

Phase I

OTHER

Placebo ( Normal Saline 0.9% Infusion Solution Bag) or active comparator (Albumin (Human) 5%, USP)

Biological: Albumin (Human) 5%, USP; Drug: Normal Saline 0.9% Infusion Solution Bag

Phase II

OTHER

Placebo ( Normal Saline 0.9% Infusion Solution Bag) or active comparator (Albumin (Human) 5%, USP), whichever was not not administered in Phase I

Biological: Albumin (Human) 5%, USP; Drug: Normal Saline 0.9% Infusion Solution Bag

Interventions

Albumin (Human) 5%, USP BIOLOGICAL

Albumin (Human) 5%, USP. Intravenous Solution. Plasma Substitute/Blood Derivative

Phase I; Phase II

Normal Saline 0.9% Infusion Solution Bag DRUG

Placebo Normal Saline 0.9% Infusion Solution Bag.

Also known as: sodium chloride 0.9% infusion solution bag

Phase I; Phase II

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, ages between 18 to 69 years
• Disease duration of \>12 months
• Diagnosis of idiopathic POTS confirmed by absolute heart rate increase to \>120 beats/minute or increase by \>30 beats/minute from baseline within 10 minutes on HUTT without orthostatic hypotension (i.e. drop in systolic BP \>30mm of Hg) Plus, • Tachycardia, associated with symptoms of orthostatic intolerance (light-headedness, palpitations, chest pain, nausea, visual blurring, sweating, limb paresthesias)
• \. Abnormal sweat testing in the leg/foot (to confirm neuropathic POTS) 2. Severe disease manifestations defined as meeting all three of the following criteria:
• Severe orthostatic intolerance - Orthostatic Symptoms Grading Scale (OSGS) Score \>12
• Severe symptoms that preclude activities of daily living i.e. Patient-Reported Outcomes Measurement Information System, Health Assessment Questionnaire (PHAQ 20) score \>36
• Lack or limited response to an adequate trial (8 weeks' duration) of at least two of the following standard treatment modalities for POTS including
• i. Increased daily intake of salt \& water ii. Midodrine iii. Fludrocortisone iv. Beta blockers v. Selective Serotonin Reuptake Inhibitors vi. Desmopressin

You may not qualify if:

• Orthostatic hypotension - a decline of 30mm Hg or more in systolic blood pressure or 20mm Hg or more in mean blood pressure within 3 minutes of standing or head-up tilt.
• Abnormal ECG or echocardiogram.
• Recent history (\<1 month) of protracted diarrhea or vomiting or hospitalization.
• History of significant psychiatric or eating disorders.
• Pregnancy or lactation.
• History of allergic reactions to human albumin.
• Patients on diuretic, laxative or antihypertensive medications (except beta blockers)
• Systemic illness affecting autonomic function (pheochromocytoma, congestive heart failure, hypertension, renal or hepatic disease, severe anemia, alcoholism, malignant neoplasm, diabetes, hypothyroidism, or stroke).
• Presence of any secondary cause of POTS - amyloidosis, sarcoidosis, alcoholism, lupus, Sjögren's syndrome, chemotherapy, and heavy metal poisoning.

Sponsors & Collaborators

• University of Alberta: lead

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Syncope; Hypotension; Tachycardia

Interventions

Albumins; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Cardiac Conduction System Disease; Pathologic Processes

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Zaeem Siddiqi, MD PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I (albumin or normal saline): 4 weeks -\> washout/crossover: 4 weeks -\>Phase II(albumin or normal saline, whichever wasn't administered in phase I): 4 weeks

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: December 7, 2017
• Study Start: January 1, 2022
• Primary Completion: October 1, 2023
• Study Completion: March 1, 2024
• Last Updated: September 19, 2024

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share