Teriparatide (Forteo) in the Treatment of Patients With Postoperative Hypocalcemia
Study Details
Study Description
Brief Summary
Primary Objective:
-To identify the optimal dose of a seven-day course of twice-daily teriparatide as compared to standard therapy for hypocalcemia in patients after total thyroidectomy and/or extensive neck dissections (pharyngectomy, laryngectomy,unilateral, bilateral / central neck, mediastinal lymph node neck dissections), with which serum calcium will be raised to corrected serum calcium levels of 8-10.5mg/dL and maintained within this range until the end of the treatment course.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Teriparatide is designed to act like a natural human hormone called parathyroid hormone, which can increase the blood levels of calcium. Calcium plus calcitriol is considered the standard treatment for low calcium in the blood.
After scheduled surgery, the level of calcium in the blood will be monitored according to the standard of care. Between 18 and 24 hours after the surgery, if calcium level drops below an acceptable level, or participants develop symptoms of low calcium, they will be randomly assigned (as in the toss of a coin) to 1 of 4 groups. One group (the "standard-of-care" group) will receive calcium plus calcitriol alone, for 7 days. The other groups (the "teriparatide" groups) will receive 1 of 3 different dose levels of teriparatide for 7 days, plus calcium and calcitriol for 7 days. There is an equal chance of getting assigned to any of these 4 groups, for the first 40 participants enrolled on this study. If enrolled after that point, participants will have a greater chance of being assigned to the group showing the best results.
Standard-of-Care Group:
If assigned to the standard-of-care group, participant will receive calcium and calcitriol according to the standard schedule and dose. The calcium will either be given through a vein or by mouth, and calcitriol will be given by mouth.
Teriparatide Group:
If assigned to a teriparatide group, participant will receive teriparatide by an injection under the skin, twice a day for 7 days. They will be taught how to perform the injections themselves, with a pen-sized device. While in the hospital, the hospital staff will watch them perform the injections and offer help, if needed. If discharged from the hospital and sent home before the 7 days of therapy are complete, they will continue giving themselves the injections (through Day 7) at home. The pen should not be removed from refrigeration for more than 2 -4 hours. Depending on what dose level of teriparatide assigned to receive, they may have to give themselves up to 3 injections each time. In addition to teriparatide, they will receive calcium and calcitriol, according to the standard schedule and dose. The calcium will either be given through a vein or by mouth, and calcitriol by mouth.
Both Groups:
If blood calcium level has not returned to normal after the 7 days of treatment, participants may need to continue receiving calcium and/or calcitriol for as long as the doctor decides it is necessary.
They will be asked to keep a medication log (diary) of when they take the teriparatide and/or calcium/calcitriol. The log should be returned to the research nurse on Day 8.
On Days 1-7, blood will be drawn to check the level of calcium twice a day (while in the hospital) or once a day (while treated as an outpatient). These blood draws (about 1 teaspoon each time) will be performed 2 hours before receiving teriparatide and/or calcium/calcitriol.
Blood will also be drawn to check calcium and parathyroid hormone levels after the study treatment is over. The first of these blood draws (about 1 tablespoon each time) will be performed at 3 days after receiving last dose of teriparatide and/or last dose of calcium/calcitriol. The second blood draw will be performed at 4 weeks after the surgery.
Starting on Day 7, and again at 4 weeks after surgery, they will be asked to collect urine over the course of a 24-hour period so calcium levels can be measured.
From Day 1 to Day 7, if discharged from the hospital and sent home, the study personnel will call on the phone once a day to see how participants are doing. At 3 days after receiving the last dose of teriparatide and/or the last dose of calcium/calcitriol, and at 4 weeks after the surgery, they will be called again.
After the urine collection, blood draw, and phone call at 4 weeks after the surgery, participation in the study is over.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Calcium + Calcitriol 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours |
Drug: Calcium
1000 milligrams by mouth (PO) Every 12 Hours
Drug: Calcitriol
0.25 micrograms PO Every 12 Hours
Other Names:
|
| Experimental: Teriparatide 20 mcg Teriparatide at 20 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours |
Drug: Teriparatide (Forteo)
Subcutaneous Injection Every 12 Hours for 7 Days
Other Names:
Drug: Calcium
1000 milligrams by mouth (PO) Every 12 Hours
Drug: Calcitriol
0.25 micrograms PO Every 12 Hours
Other Names:
|
| Experimental: Teriparatide 40 mcg Teriparatide at 40 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours |
Drug: Teriparatide (Forteo)
Subcutaneous Injection Every 12 Hours for 7 Days
Other Names:
Drug: Calcium
1000 milligrams by mouth (PO) Every 12 Hours
Drug: Calcitriol
0.25 micrograms PO Every 12 Hours
Other Names:
|
| Experimental: Teriparatide 60 mcg Teriparatide at 60 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours |
Drug: Teriparatide (Forteo)
Subcutaneous Injection Every 12 Hours for 7 Days
Other Names:
Drug: Calcium
1000 milligrams by mouth (PO) Every 12 Hours
Drug: Calcitriol
0.25 micrograms PO Every 12 Hours
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Success [2 - 7 days post-treatment]
A patient "success" is defined as a normal calcium level (Ca>=8 and Ca<= 10.5) within 48 hours post-treatment initiation and a normal Ca level maintained through day 7 post-treatment initiation.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients who are scheduled for total thyroidectomy, and/or extensive neck dissections (pharyngectomy, laryngectomy, unilateral/bilateral/central neck, and/or mediastinal lymph node neck dissections).
-
Patients who develop, between 18-24 hours after surgery, hypocalcemia as defined by a corrected serum calcium <8.0mg/dL. [Corrected serum calcium (mg/dL) = Measured calcium
- (4-albumin) x 0.8]
Exclusion Criteria:
-
Patients who have jejunal tubes
-
Patients <18 years old.
-
Treatment with teriparatide or calcitriol (Rocaltrol) within 1 month prior to surgery
-
Treatment with a bisphosphonate within 3 months prior to surgery
-
Hypercalcemia (corrected serum calcium >10.5mg/dL) or hypocalcemia (corrected serum calcium <8.4mg/dL) on preoperative labs (drawn within 21 days of surgery)
-
Paget's disease of bone
-
Elevated alkaline phosphatase > institutional upper limit of normal (ULN)
-
History of external beam irradiation to the skeleton
-
History of skeletal metastases
-
History of untreated gout
-
History of unstable angina pectoris
-
History of symptomatic orthostatic hypotension
-
Pregnancy (as screened by a serum/urine pregnancy test) or breast-feeding. Female subjects of childbearing potential must have a negative pregnancy test within 7 days of surgery. Postmenopausal women (absence of menses for 12 months) or women with history of hysterectomy or bilateral oophorectomy will not be required to have a pregnancy test. Male and female patients of reproductive potential must agree to utilize an effective form of contraception throughout the study period. The definition of effective contraception will be based on the judgment of the Investigator or designated associate.
-
Hepatic and renal dysfunction defined by the following parameters: (a) Serum AST (SGOT) and ALT (SGPT) > 3 times the institutional ULN, (b) Total serum bilirubin > 2 times the institutional ULN, (c) Serum creatinine > 1.5mg/dL or estimated creatinine clearance < 40mL/min
-
Psychiatric illness or social situation that would limit compliance with study requirements
-
Concomitant use of digoxin
-
Patients may not be receiving any other investigational agents or have participated in any investigational drug study within 28 days preceding the start of study treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UT MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- Eli Lilly and Company
Investigators
- Principal Investigator: Mimi Hu, MD, UT MD Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2006-0562
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: May 2, 2008 to April 13, 2009. All recruitment done at UT MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail | A total of 7 patients were consented and screened. None of the patients met study entry criteria and thus were not randomized to treatment. Due to slow accrual, the study was closed. |
| Arm/Group Title | Calcium + Calcitriol | Teriparatide 20 Mcg | Teriparatide 40 Mcg | Teriparatide 60 Mcg |
|---|---|---|---|---|
| Arm/Group Description | 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 20 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 40 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 60 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours |
| Period Title: Overall Study | ||||
| STARTED | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Calcium + Calcitriol | Teriparatide 20 Mcg | Teriparatide 40 Mcg | Teriparatide 60 Mcg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 20 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 40 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 60 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Total of all reporting groups |
| Overall Participants | 0 | 0 | 0 | 0 | 0 |
| Age (years) [Median (Full Range) ] | |||||
| Sex: Female, Male (Count of Participants) | |||||
| Region of Enrollment (participants) [Number] | |||||
Outcome Measures
| Title | Number of Patients With Success |
|---|---|
| Description | A patient "success" is defined as a normal calcium level (Ca>=8 and Ca<= 10.5) within 48 hours post-treatment initiation and a normal Ca level maintained through day 7 post-treatment initiation. |
| Time Frame | 2 - 7 days post-treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Terminated due low accrual, none of 7 participants met eligibility criteria therefore not treated nor randomized to study arms. |
| Arm/Group Title | Calcium + Calcitriol | Teriparatide 20 Mcg | Teriparatide 40 Mcg | Teriparatide 60 Mcg |
|---|---|---|---|---|
| Arm/Group Description | 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 20 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 40 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 60 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours |
| Measure Participants | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | Study period 1 Year | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | As no patient received study treatment, neither adverse events nor serious adverse events have occurred. | |||||||
| Arm/Group Title | Calcium + Calcitriol | Teriparatide 20 Mcg | Teriparatide 40 Mcg | Teriparatide 60 Mcg | ||||
| Arm/Group Description | 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 20 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 40 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | Teriparatide at 60 mcg; and 1000 milligrams Calcium + 0.25 micrograms Calcitriol orally every 12 hours | ||||
All Cause Mortality |
||||||||
| Calcium + Calcitriol | Teriparatide 20 Mcg | Teriparatide 40 Mcg | Teriparatide 60 Mcg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Calcium + Calcitriol | Teriparatide 20 Mcg | Teriparatide 40 Mcg | Teriparatide 60 Mcg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Calcium + Calcitriol | Teriparatide 20 Mcg | Teriparatide 40 Mcg | Teriparatide 60 Mcg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | 0/0 (NaN) | ||||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Mimi Hu, MD / Professor |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | |
| CR_Study_Registration@mdanderson.org |
- 2006-0562