Trial Outcomes & Findings for A Pilot Clinical Study Evaluating the Effect of Parathyroid Hormone (PTH) Lowering On Erythropoietin Consumption in Calcitriol-Resistant Patients (NCT NCT01506947)

Last Updated: 2021-07-30

Results Overview

The requirement of erythropoietin (EPO) treatment to maintain serum hemoglobin levels between 10 to 11.5 g/dL during the study was assessed by analysis of the dose of darbepoetin alfa used at baseline and during each month of the study. The mean EPO dosage per injection for each study month is reported.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

65 participants

Primary outcome timeframe

Baseline and Months 1, 2, 3, 4, 5 and 6

Results posted on

2021-07-30

Participant Flow

This study was conducted at 7 centers in Turkey.

Participant milestones

Participant milestones
Measure	Paricalcitol Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.
Overall Study STARTED	65
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Paricalcitol Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.
Overall Study Lost to Follow-up	7
Overall Study Adverse Event	5
Overall Study Death	1
Overall Study Did Not Meet Eligibility Criteria	3

Baseline Characteristics

A Pilot Clinical Study Evaluating the Effect of Parathyroid Hormone (PTH) Lowering On Erythropoietin Consumption in Calcitriol-Resistant Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.
Age, Continuous	49.6 years STANDARD_DEVIATION 16.7 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Months 1, 2, 3, 4, 5 and 6

Population: Per-protocol analysis set with EPO dosage available at all visits.

Outcome measures

Outcome measures
Measure	Paricalcitol n=45 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Mean Erythropoietin Dose Per Visit Baseline	35.8 µg Standard Deviation 15.0	—
Mean Erythropoietin Dose Per Visit Month 1	22.2 µg Standard Deviation 20.0	—
Mean Erythropoietin Dose Per Visit Month 2	22.7 µg Standard Deviation 21.3	—
Mean Erythropoietin Dose Per Visit Month 3	4.7 µg Standard Deviation 4.5	—
Mean Erythropoietin Dose Per Visit Month 4	7.2 µg Standard Deviation 6.2	—
Mean Erythropoietin Dose Per Visit Month 5	17.3 µg Standard Deviation 19.5	—
Mean Erythropoietin Dose Per Visit Month 6	21.8 µg Standard Deviation 19.7	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: Per-protocol analysis set

The Medical Outcome Study Short Form 36-Item Health Survey (SF-36) is a self-administered questionnaire that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains. The domains include physical (physical functioning, role limitations due to physical health (role-physical), general health perceptions and pain) and mental domains (energy/fatigue (vitality), social functioning, emotional well-being (mental health), and role limitations due to emotional problems (role emotional)). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.

Outcome measures

Outcome measures
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Physical Function - Baseline	51.7 units on a scale Standard Deviation 26.3	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Physical Function - Month 6	51.5 units on a scale Standard Deviation 30.1	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Role Physical - Baseline	38.5 units on a scale Standard Deviation 45.2	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Role Physical - Month 6	44.3 units on a scale Standard Deviation 46.5	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Role Emotional - Baseline	52.8 units on a scale Standard Deviation 46.0	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Role Emotional - Month 6	54.2 units on a scale Standard Deviation 47.0	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Vitality - Baseline	47.4 units on a scale Standard Deviation 16.5	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Vitality - Month 6	45.2 units on a scale Standard Deviation 17.0	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Mental Health - Baseline	54.5 units on a scale Standard Deviation 12.6	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Mental Health - Month 6	52.7 units on a scale Standard Deviation 15.2	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Social Functioning - Baseline	59.6 units on a scale Standard Deviation 20.7	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Social Functioning - Month 6	55.5 units on a scale Standard Deviation 26.3	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Pain - Baseline	61.3 units on a scale Standard Deviation 26.6	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire Pain - Month 6	60.5 units on a scale Standard Deviation 25.0	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire General Health - Baseline	47.0 units on a scale Standard Deviation 16.9	—
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire General Health - Month 6	44.4 units on a scale Standard Deviation 22.3	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: Per-protocol analysis set with available data at each time point.

Outcome measures

Outcome measures
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Mean Intact Parathyroid Hormone (iPTH) Level at Baseline and Month 6 Baseline	918.0 pg/mL Standard Deviation 585.9	—
Mean Intact Parathyroid Hormone (iPTH) Level at Baseline and Month 6 Month 6	692.5 pg/mL Standard Deviation 413.4	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: Per-protocol analysis set with available data at each time point.

Outcome measures

Outcome measures
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Mean Calcium Level at Baseline and Month 6 Baseline	8.81 mg/mL Standard Deviation 0.95	—
Mean Calcium Level at Baseline and Month 6 Month 6	9.29 mg/mL Standard Deviation 0.86	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: Participants who completed the study with available data at each time point.

Outcome measures

Outcome measures
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Mean Phosphorus Level at Baseline and Month 6 Baseline	4.87 mg/mL Standard Deviation 1.11	—
Mean Phosphorus Level at Baseline and Month 6 Month 6	5.47 mg/mL Standard Deviation 1.22	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: Per-protocol analysis set with available data at each time point.

Outcome measures

Outcome measures
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Mean Alkaline Phosphatase Level at Baseline and Month 6 Baseline	225.7 U/L Standard Deviation 170.1	—
Mean Alkaline Phosphatase Level at Baseline and Month 6 Month 6	172.9 U/L Standard Deviation 147.6	—

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Per-protocol analysis set with available data at each time point.

Vitamin B12 levels were categorized according to the following laboratory reference ranges: Low: \< 200 pg/mL Normal: 200 - 950 pg/mL High: \> 950 pg/mL

Outcome measures

Outcome measures
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6 n=46 Participants
Vitamin B12 Levels Low	2 Participants	0 Participants
Vitamin B12 Levels Normal	13 Participants	22 Participants
Vitamin B12 Levels High	33 Participants	24 Participants

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Per-protocol analysis set with available data at each time point.

Folic acid levels were categorized according to the following laboratory reference ranges: Low: \< 4.6 ng/mL Normal: 4.6 - 18.7 ng/mL High: \> 18.7 ng/mL

Outcome measures

Outcome measures
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6 n=46 Participants
Folic Acid Levels Low	1 Participants	4 Participants
Folic Acid Levels Normal	25 Participants	25 Participants
Folic Acid Levels High	22 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: Per-protocol analysis set with available data at each time point.

Outcome measures

Outcome measures
Measure	Paricalcitol n=48 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Mean High Sensitivity C-reactive Protein (hsCRP) Level at Baseline and Month 6 Baseline	11.8 mg/mL Standard Deviation 14.1	—
Mean High Sensitivity C-reactive Protein (hsCRP) Level at Baseline and Month 6 Month 6	14.4 mg/mL Standard Deviation 20.7	—

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: Per-protocol analysis set with available data at each time point.

Outcome measures

Outcome measures
Measure	Paricalcitol n=46 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Mean Fibroblast Growth Factor-23 (FGF-23) Level at Baseline and Month 6 Month 6	11340 kRU/L Standard Deviation 13450	—
Mean Fibroblast Growth Factor-23 (FGF-23) Level at Baseline and Month 6 Baseline	6267 kRU/L Standard Deviation 5967	—

SECONDARY outcome

Timeframe: From the time of study drug administration until 4 weeks after the discontinuation of the study drug; up to 7 months.

Population: The safety population included all participants who enrolled.

Serious adverse events were any adverse events meeting any of the following criteria: * An event that resulted in the death of a participant; * An event that, in the opinion of the investigator, would have resulted in immediate fatality if medical intervention had not been taken (life-threatening); * Resulted in an admission to the hospital for any length of time or prolonged hospital stay; * An anomaly detected at or after birth, or any anomaly that results in fetal loss; * An event that resulted in a condition that substantially interfered with the activities of daily living; * An important medical event that may not be immediately life-threatening or result in death or hospitalization, but based on medical judgment may have jeopardized the participant and may have required medical or surgical intervention to prevent any of the outcomes listed above. Adverse events were assessed by the investigator for possible relationship to study drug.

Outcome measures

Outcome measures
Measure	Paricalcitol n=65 Participants Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.	Month 6
Number of Participants With Adverse Events Non-serious adverse events	9 participants	—
Number of Participants With Adverse Events Serious adverse events	11 participants	—
Number of Participants With Adverse Events Treatment-related adverse events	0 participants	—
Number of Participants With Adverse Events Fatal adverse events	3 participants	—

Adverse Events

Paricalcitol

Serious events: 11 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Paricalcitol n=65 participants at risk Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.
Surgical and medical procedures Nephrectomy	1.5% 1/65 • 6 months
General disorders Asthenia	3.1% 2/65 • 6 months
General disorders Fatigue	1.5% 1/65 • 6 months
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.5% 1/65 • 6 months
Gastrointestinal disorders Ascites	1.5% 1/65 • 6 months
Metabolism and nutrition disorders Hyperkalaemia	1.5% 1/65 • 6 months
Cardiac disorders Cardio-respiratory arrest	1.5% 1/65 • 6 months
Surgical and medical procedures Parathyroidectomy	1.5% 1/65 • 6 months
Surgical and medical procedures Renal transplant	3.1% 2/65 • 6 months
Infections and infestations Soft tissue infection	1.5% 1/65 • 6 months
General disorders Pyrexia	3.1% 2/65 • 6 months
Injury, poisoning and procedural complications Arteriovenous fistula site complication	1.5% 1/65 • 6 months
Skin and subcutaneous tissue disorders Erythema	1.5% 1/65 • 6 months
Cardiac disorders Acute coronary syndrome	1.5% 1/65 • 6 months
Infections and infestations Lung infection	1.5% 1/65 • 6 months
General disorders Chest Pain	1.5% 1/65 • 6 months
Respiratory, thoracic and mediastinal disorders Productive cough	1.5% 1/65 • 6 months
Respiratory, thoracic and mediastinal disorders Cough	1.5% 1/65 • 6 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.2% 4/65 • 6 months
Cardiac disorders Palpitations	3.1% 2/65 • 6 months
Skin and subcutaneous tissue disorders Diabetic foot	1.5% 1/65 • 6 months
Respiratory, thoracic and mediastinal disorders Acute Respiratory distress syndrome	1.5% 1/65 • 6 months
Nervous system disorders Loss of consciousness	1.5% 1/65 • 6 months
Respiratory, thoracic and mediastinal disorders Respiratory arrest	1.5% 1/65 • 6 months
Cardiac disorders Cardiac valve disease	1.5% 1/65 • 6 months
Cardiac disorders Arrhythmia	1.5% 1/65 • 6 months
Infections and infestations Respiratory Tract Infection	1.5% 1/65 • 6 months
Cardiac disorders Mitral valve incompetence	1.5% 1/65 • 6 months
Nervous system disorders Somnolence	1.5% 1/65 • 6 months
Nervous system disorders Cerebrovascular Accident	1.5% 1/65 • 6 months
Gastrointestinal disorders Abdominal pain upper	1.5% 1/65 • 6 months
Gastrointestinal disorders Stools watery	1.5% 1/65 • 6 months
Gastrointestinal disorders Faeces discoloured	1.5% 1/65 • 6 months
Investigations Haemoglobin decreased	1.5% 1/65 • 6 months
Gastrointestinal disorders Gastric ulcer	1.5% 1/65 • 6 months
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.5% 1/65 • 6 months
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	3.1% 2/65 • 6 months
Blood and lymphatic system disorders Haemoconcentration	1.5% 1/65 • 6 months
Investigations Haemoglobin increased	1.5% 1/65 • 6 months

Other adverse events

Other adverse events
Measure	Paricalcitol n=65 participants at risk Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia.
Injury, poisoning and procedural complications Arteriovenous fistula site haemorrhage	1.5% 1/65 • 6 months
Infections and infestations Nasopharyngitis	1.5% 1/65 • 6 months
Vascular disorders Arteriovenous fistula	1.5% 1/65 • 6 months
Nervous system disorders Headache	1.5% 1/65 • 6 months
Respiratory, thoracic and mediastinal disorders Epistaxis	1.5% 1/65 • 6 months
Skin and subcutaneous tissue disorders Hyperhidrosis	1.5% 1/65 • 6 months
Ear and labyrinth disorders Vertigo	1.5% 1/65 • 6 months
Nervous system disorders Dizziness	1.5% 1/65 • 6 months
General disorders Chest pain	1.5% 1/65 • 6 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.5% 1/65 • 6 months
General disorders Pain	1.5% 1/65 • 6 months
Musculoskeletal and connective tissue disorders Myalgia	1.5% 1/65 • 6 months
Gastrointestinal disorders Abdominal pain upper	1.5% 1/65 • 6 months
Gastrointestinal disorders Nausea	1.5% 1/65 • 6 months
Gastrointestinal disorders Gastric haemorrhage	1.5% 1/65 • 6 months

Additional Information

Global Medical Services

AbbVie (prior sponsor Abbott)

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER